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Ying Ru Feng,1 Lynn Meuleners,1 Mark Stevenson,2,3 Jane Heyworth,4 Kevin Murray,4 Michelle Fraser,1 Sean Maher5 1Western Australian Centre for Road Safety Research, School of Population and Global Health, The University of Western Australia, Perth, WA, Australia; 2Transport, Health and Urban Design Research Lab, Melbourne School of Design, University of Melbourne, Melbourne, VIC, Australia; 3Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia; 4School of Population and Global Health, The University of Western Australia, Crawley, WA, 6009, Australia; 5Department of Rehabilitation and Aged Care, Sir Charles Gairdner Hospital, Perth, WA, AustraliaCorrespondence: Lynn MeulenersWestern Australian Centre for Road Safety Research, School of Population and Global Health, The University of Western Australia (M431), 35 Stirling Hwy, Perth, WA, 6009, AustraliaTel +61 8 6488 7375Email lynn.meuleners@uwa.edu.auPurpose: Mild cognitive impairment can impact driving performance and self-regulation practices. However, there is little evidence on how cognitive impairment may impact these self-regulation practices over a period of time. Therefore, the aim of this study was to examine changes in the number and type of situations in which older drivers with and without suspected mild cognitive impairment (MCI) self-regulate their driving over a one-year period, after accounting for relevant confounders.Participants and Methods: A longitudinal cohort study involving older drivers (65+ years) from metropolitan Western Australia was interviewed by a telephone interview at baseline and one-year follow-up. The Telephone Cognitive Screen (T-CogS) was also administered to determine changes in their cognitive status. The outcome of interest was the number and type of situations older drivers self-regulated their driving.Results: A total of 670 drivers were interviewed at baseline (suspected MCI: n = 227; no cognitive impairment: n = 443) and one-year follow-up (suspected MCI: n = 251; no cognitive impairment: n = 419), which provided 1340 observations. Drivers with suspected MCI increased the number of driving situations in which they self-regulated by 13% over a period of one-year compared with drivers without cognitive impairment (IRR = 1.13, 95% CI = 1.02– 1.27, p = 0.025). Specifically, drivers with suspected MCI had 60% increased odds of self-regulating when “making turns across oncoming traffic” compared with drivers without cognitive impairment (unadjusted OR = 1.60, 95% CI = 1.02– 2.53, p = 0.041). Other significant factors included being female (IRR = 1.87, 95% = 1.52– 2.32, p = 0.001), aged 75+ years (IRR = 1.33, 95% CI = 1.10– 1.60, p = 0.003), higher number of comorbidities (1– 3 comorbidities: IRR = 1.26, 95% CI = 1.01– 1.58, p = 0.040; 4+ comorbidities: IRR = 1.39, 95% CI = 1.08– 1.78, p = 0.011), “decreased driving confidence” (IRR = 1.32, 95% CI = 1.10– 1.58, p-value = 0.003) and “preference of having someone else drive” (IRR = 1.38, 95% CI = 1.12– 1.70, p = 0.003). Having one or more traffic infringements was also associated with a decrease in the number of self-regulated driving situations (IRR = 0.80, 95% CI = 0.67– 0.95, p = 0.011).Conclusion: Over a one-year period, drivers with suspected MCI increased the number of situations in which they self-regulated their driving compared with drivers without cognitive impairment, particularly when “making turns across oncoming traffic”. Future studies should examine whether this increase in the types and number of self-regulated driving situations is enough to compensate for declines in cognition.Keywords: longitudinal, cognitive decline, driving behaviour, driving restriction, driving patterns

Ying Ru Feng,1 Lynn Meuleners,1 Mark Stevenson,2,3 Jane Heyworth,4 Kevin Murray,4 Michelle Fraser,1 Sean Maher5 1Western Australian Centre for Road Safety Research, School of Population and Global Health, The University of Western Australia, Perth, WA, Australia; 2Transport, Health and Urban Design Research Lab, Melbourne School of Design, University of Melbourne, Melbourne, VIC, Australia; 3Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia; 4School of Population and Global Health, The University of Western Australia, Crawley, WA, 6009, Australia; 5Department of Rehabilitation and Aged Care, Sir Charles Gairdner Hospital, Perth, WA, AustraliaCorrespondence: Lynn MeulenersWestern Australian Centre for Road Safety Research, School of Population and Global Health, The University of Western Australia (M431), 35 Stirling Highway, Crawley, WA, 6009, AustraliaTel +61 8 6488 7375Email lynn.meuleners@uwa.edu.auPurpose: Mild cognitive impairment and gender can impact different aspects of driving performance and behaviour in older drivers. However, there is little evidence on how these may affect naturalistic speeding behaviour. Therefore, the aim of this study was to examine the relationship between speeding events and cognitive status for older male and female drivers.Participants and Methods: A naturalistic driving study collected objective driving information over a two-week period using an in-vehicle monitoring device from 36 older drivers with suspected mild cognitive impairment and 35 older drivers without cognitive impairment. The outcome of interest examined was the number of speeding events, defined as travelling 5+ km/h over the posted speed limit for at least a minute.Results: The majority of participants (n=58, 81.69%) did not have a speeding event during the two-week monitoring period. Twenty-three speeding events were recorded among seven drivers with suspected mild cognitive impairment and six drivers without cognitive impairment. The majority of speeding events (82.61%) were by older male drivers and occurred in 60km/h and 70km/h speed zones. The results of the two negative binomial regression models found that in older male drivers, suspected mild cognitive impairment (IRR=7.45, 95% CI=1.53– 36.15, p=0.01) was associated with a significantly higher rate of speeding events, while increasing age was associated with a lower rate of speeding events (IRR=0.80, 95% CI=0.64– 1.00, p=0.04). For older female drivers, there were no factors significantly associated with the rate of speeding events.Conclusion: While the overall number of speeding events were infrequent, suspected mild cognitive impairment was associated with a significant increase in the rate of speeding events for older male drivers, but not for older female drivers. Speeding interventions and injury prevention policy strategies may need to be targeted differently for male and female drivers with mild cognitive impairment.Keywords: naturalistic, driver monitoring, cognitive decline, gender differences, driving behaviour

Ying Ru Feng,1 Lynn Meuleners,1 Mark Stevenson,2,3 Jane Heyworth,1 Kevin Murray,1 Sean Maher4 1School of Population and Global Health, The University of Western Australia, Perth, WA, Australia; 2Transport, Health and Urban Design, Melbourne School of Design, University of Melbourne, Melbourne, VIC, Australia; 3Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia; 4Department of Rehabilitation and Aged Care, Sir Charles Gairdner Hospital, Perth, WA, AustraliaCorrespondence: Lynn MeulenersSchool of Population and Global Health, The University of Western Australia (M431), 35 Stirling Hwy, Crawley, Perth, WA 6009, AustraliaTel +61 8 6488 7375Email lynn.meuleners@uwa.edu.auObjective: To assess the impact of cognitive, socio-demographic and driving-related characteristics on self-regulation practices in older drivers with mild cognitive impairment (MCI) (determined by the Telephone Cognitive Screen (T-CogS) score), compared with drivers with no cognitive impairment.Design, Setting, Participants: A cross-sectional study collected information from 362 drivers with MCI and 611 drivers with no cognitive impairment, who were aged 65+ years, and were living in Western Australia between November 2018 and February 2019.Measurements: Self-reported self-regulation driving practices.Results: The majority of drivers with MCI (62.4%) and those with no cognitive impairment (57.1%) reported self-regulating their driving in at least one situation, in the past three months. The most common situations that both groups of drivers self-regulated in were “driving at night in the rain”, “parallel parking”, and “driving when raining”. Drivers with MCI were only significantly more likely to self-regulate when “making turns across oncoming traffic” and “driving at night”. They also had 39% greater odds of self-regulating in at least one driving situation, compared with drivers with no cognitive impairment (OR: 1.39, 95% CI=1.04– 1.85, p=0.02). Females also had 2.3 times greater odds of self-regulating (OR=2.34, 95% CI=1.76– 3.12, p< 0.001). Drivers aged 75+ years had 1.6 times greater odds of self-regulating, compared with drivers aged 65– 69 years (OR=1.58, 95% CI=1.12– 2.23, p=0.01).Conclusion: Older drivers with MCI were more likely to self-regulate their driving, compared to drivers with no cognitive impairment, particularly in complex driving situations. This suggests that some drivers with MCI may be able to recognize their cognitive limitations and adjust their driving accordingly. However, several drivers with MCI, particularly males, did not self-regulate their driving. This highlights the importance of advising patients about the impact of MCI on driving ability, suitable self-regulation strategies, as well as monitoring their driving ability.Keywords: driving, aging, self-regulation, older drivers, mild cognitive impairment

Ying Ru Feng,1,2 Lynn B Meuleners,2 Michelle L Fraser,2 Kate J Brameld,2 Seraina Agramunt2 1School of Population and Global Health, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA, Australia; 2Curtin-Monash Accident Research Centre (C-MARC), Faculty of Health Sciences, Curtin University, Perth, WA, Australia Purpose: The purpose of this study was to investigate the impact of the first and second eye cataract surgeries on the risk of falls in participants with bilateral cataract and to determine which changes in visual measures are associated with changes in the number of falls throughout the cataract surgery process.Patients and methods: Fifty-five older adults with bilateral cataract aged 55+ years were assessed at three time points during the cataract surgery process, and they completed a falls diary. Two separate generalized estimating equation–negative binomial models were undertaken to assess changes in the number of falls before first eye cataract surgery, between first and second eye surgeries, and after second eye cataract surgery and which changes in visual measures were associated with changes in the number of falls.Results: After adjusting for potential confounding factors, the risk of falls decreased by 54% (incidence rate ratio (IRR) =0.458, 95% CI=0.215–0.974, p=0.04) after first eye cataract surgery only, compared with the period before first eye surgery. The risk of falls decreased by 73% (IRR =0.268, 95% CI =0.114–0.628, p=0.002) after second eye cataract surgery, compared with the period before first eye surgery. Improved binocular visual acuity (IRR =5.488, 95% CI =1.191–25.282, p=0.029) and contrast sensitivity (IRR =0.257, 95% CI =0.070–0.939, p=0.040) were associated with a decrease in the number of falls.Conclusion: The study found that first and second eye cataract surgeries reduced the risk of falls among a cohort of bilateral cataract patients with relatively good baseline vision. This suggests that timely first and second eye cataract surgeries could play an important role in reducing the burden due to falls among older adults with cataract. Keywords: vision, bilateral cataract, older population, injuries

Issue Addressed: It is unknown whether SunSmart health promotion campaigns in Western Australia are still effectively reaching their target audience of young people (under 45 years). This study examined trends over time in awareness, relevancy and believability of SunSmart advertisements and identified socio-demographic characteristics and risk factors associated with campaign awareness., Method: Linear regression and log-binomial modelling were undertaken using data from the annual SunSmart post-campaign evaluation surveys between 2008/2009 and 2021/2022. SunSmart campaigns were analysed and categorised into the following themes: (1) personal real-life stories; (2) daily activities/sun exposure leads to skin cancer; or (3) cartoon/animated., Results: Between 2008 and 2022, there were declines in total awareness (74.2% to 20.4%), unprompted awareness (33.7% to 4.9%) and relevancy (89.5% to 54.8%) of SunSmart advertisements (representing annual percent decreases of 3.6%, 3.1% and 1.8%, respectively). However, believability remained high over time (>94% in each annual survey). Trends were inconsistent between the awareness of campaign themes and socio-demographic characteristics and risk factors. Several campaigns had greater awareness in their subsequent years, compared with the first campaign year., Conclusion: In more recent years, SunSmart advertisements and campaigns may not have reached their target audience. In addition to socio-demographic characteristics, particularly age, advertisement factors may also affect the awareness of specific campaigns. SO WHAT?: Given the changing advertising landscape and its rising costs, ongoing funding is pertinent to increase the reach of future SunSmart campaigns. Increasing advertisements on alternative platforms and designing campaigns which separately target adolescents and adults need to be considered., (© 2024 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Background: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research., Methods: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay., Results: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels., Conclusion: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes., (© 2024. Children's Hospital, Zhejiang University School of Medicine.)

Equid alphaherpesvirus 1 (EHV-1) has been linked to the emergence of neurological disorders, with the horse racing industry experiencing significant impacts from outbreaks of equine herpesvirus myeloencephalopathy (EHM). Building robust immune memory before pathogen exposure enables rapid recognition and elimination, preventing infection. This is crucial for effectively managing EHV-1. Removing neuropathogenic factors and immune evasion genes to develop live attenuated vaccines appears to be a successful strategy for EHV-1 vaccines. We created mutant viruses without ORF38 and ORF37/38 and validated their neuropathogenicity and immunogenicity in hamsters. The ∆ORF38 strain caused brain tissue damage at high doses, whereas the ∆ORF37/38 strain did not. Dexamethasone was used to confirm latent herpesvirus infection and reactivation. Dexamethasone injection increased viral DNA load in the brains of hamsters infected with the parental and ∆ORF38 strains, but not in those infected with the ∆ORF37/38 strain. Immunizing hamsters intranasally with the ∆ORF37/38 strain as a live vaccine produced a stronger immune response compared to the ∆ORF38 strain at the same dose. The hamsters demonstrated effective protection against a lethal challenge with the parental strain. This suggests that the deletion of ORF37/38 may effectively inhibit latent viral infection, reduce the neuropathogenicity of EHV-1, and induce a protective immune response.

This study examined changes in physical and mental health quality-of-life and health services access before and after the onset of the COVID-19 pandemic among individuals of lower and higher socio-economic status (SES) in Australia. Difference-in-differences and logistic regression models were undertaken using data from the Household, Income and Labour Dynamics in Australia (HILDA) survey and government data on COVID-19 lockdowns between January 2020 and February 2021. Individuals from higher SES reported larger decreases in mental health quality-of-life scores than those from lower SES after the onset of the pandemic. Those from lower SES reported less disruption with any health services (24.2% vs 30.4%; OR = 0.68; p < 0.001), specifically dental services (8.2% vs 15.4%; OR = 0.51; p < 0.001) and allied health services (5.9% vs 8.5%; OR = 0.60; p < 0.001), compared with those from higher SES. Additional days under lockdown were associated with reduced access to all health services (OR = 1.19). Furthermore, long-term health conditions (higher SES: OR = 1.54) and scores indicative of poorer physical (lower SES: OR = 1.17; higher SES: OR = 1.07) and mental health (lower SES: OR = 1.16; higher SES: OR = 1.12) were associated with increased health services disruption. While individuals from higher SES were more likely than those from lower SES to experience greater relative declines in mental health and increased disruption with health services access, individuals with a greater apparent need for health services, regardless of SES, may have faced inequalities in accessing these services during the COVID-19 pandemic., (© The Author(s) 2024. Published by Oxford University Press.)

Climate change is resulting in more frequent and rapidly changing temperatures at both extremes that severely affect the growth and production of plants, particularly crops. Oxidative stress caused by high temperatures is one of the most damaging factors for plants. However, the role of hydrogen peroxide (H 2 O 2 ) in modulating plant thermotolerance is largely unknown, and the regulation of photorespiration essential for C3 species remains to be fully clarified. Here, we report that heat stress promotes H 2 O 2 accumulation in chloroplasts and that H 2 O 2 stimulates sulfenylation of the chloroplast-localized photorespiratory enzyme 2-phosphoglycolate phosphatase 1 (PGLP1) at cysteine 86, inhibiting its activity and promoting the accumulation of the toxic metabolite 2-phosphoglycolate. We also demonstrate that PGLP1 has a positive function in plant thermotolerance, as PGLP1 antisense lines have greater heat sensitivity and PGLP1-overexpressing plants have higher heat-stress tolerance than the wild type. Together, our results demonstrate that heat-induced H 2 O 2 in chloroplasts sulfenylates and inhibits PGLP1 to modulate plant thermotolerance. Furthermore, targeting CATALASE2 to chloroplasts can largely prevent the heat-induced overaccumulation of H 2 O 2 and the sulfenylation of PGLP1, thus conferring thermotolerance without a plant growth penalty. These findings reveal that heat-induced H 2 O 2 in chloroplasts is important for heat-caused plant damage., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the levels of serum folate and vitamin B 12 (VB 12 ) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD)., Methods: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB 12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment., Results: The levels of serum folate and VB 12 in ASD children were significantly lower than those in healthy children ( P <0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients ( P <0.05), and serum VB 12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients ( P <0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains ( P <0.05), and serum VB 12 levels were positively correlated with language developmental quotient ( P <0.05). In male ASD children, serum VB 12 levels were positively correlated with language and personal-social developmental quotients ( P <0.05)., Conclusions: Serum folate and VB 12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB 12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.

Background: LanGui tea, a traditional Chinese medicine formulation comprising of Gynostemma pentaphyllum (Thunb.) Makino, Cinnamomum cassia (L.) J. Presl, and Ampelopsis grossedentata (Hand-Mazz) W.T. Wang, has yet to have its potential contributions to alcoholic liver disease (ALD) fully elucidated. Consequently, the objective of this research is to investigate the protective properties of LanGui tea against binge alcohol-induced ALD and the mechanisms underlying its effects., Methods: An experimental model of acute alcohol-induced liver disease was performed to assess the protective effects of extract of LanGui tea (ELG) at both 50 and 100 mg.kg -1 dosages on male C57BL/6 mice. Various parameters, including hepatic histological changes, inflammation, lipids content, as well as liver enzymes and interleukin 1β (IL-1β) in the serum were measured. The pharmacological mechanisms of ELG, specifically its effects on adenosine monophosphate-(AMP)-activated protein kinase (AMPK) and NLR family pyrin domain containing 3 (NLRP3) signaling, were investigated through Western blotting, qRT-PCR, ELISA, immunohistochemistry, immunofluorescence analyses, and by blocking the AMPK activity., Results: ELG demonstrated a mitigating effect on fatty liver, inflammation, and hepatic dysfunction within the mouse model. This effect was achieved by activating AMPK signaling and inhibitingNLRP3 signaling in the liver, causing a reduction in IL-1β generation. In vitro studies further confirmed that ELG inhibited cell damage and IL-1β production in ethanol-induced hepatocytes by enhancing AMPK-NLRP3 signaling. Conversely, the pharmacological inhibition of AMPK activity nearly abrogated such alteration., Conclusions: Thus, LanGui tea emerges as a promising herbal therapy for ALD management involving AMPK-NLRP3 signaling., (© 2024. The Author(s).)

Background: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation., Methods: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method., Discussion: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits., Trial Registration: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022)., (© 2024. The Author(s).)

Introduction: Hormone replacement treatment (HRT) is the most commonly used endometrial preparation protocol for frozen embryo transfer (FET) in patients with polycystic ovary syndrome (PCOS). However, studies have found that HRT may increase the risk of hypertensive disorders of pregnancy and some obstetric complications. Letrozole is a new first-line ovulation induction drug for PCOS and can effectively induce spontaneous ovulation by reducing oestrogen levels. However, letrozole is still rarely used in FET and has only been reported in a few studies in Asian populations. High-quality, well-powered randomised controlled trials (RCTs) comparing HRT and letrozole-stimulated protocols are lacking. The aim of this study is to compare the efficacy and safety of two protocols in patients with PCOS., Methods and Analysis: This is a multicentre, open-label RCT in four reproductive medical centres in China. In total, 1078 women with PCOS will be randomised (1:1) to the letrozole-stimulated or HRT group in their first FET cycle and their pregnancy and perinatal outcomes during this cycle will be followed up and analysed. The primary outcome is live birth. Secondary outcomes are cycle cancellation rate, biochemical pregnancy, clinical pregnancy, miscarriage, ectopic pregnancy, obstetric and perinatal complications, neonatal complications and birth weight., Ethics and Dissemination: Ethical approval was obtained from the Institutional Review Board of Reproductive and Genetic Hospital of CITIC-XIANGYA (LL-SC-2022-001). Written informed consent will be obtained from each participant. The findings will be disseminated through conference presentations and publication in peer-reviewed journals., Trial Registration Number: NCT05227391., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To analyze the difference in blood uric acid levels between patients with polycystic ovary syndrome (PCOS) and healthy women of childbearing age, and to investigate the correlation between body composition and blood uric acid levels. Methods: A total of 153 eligible childbearing age patients with PCOS treated at Tianjin Medical University General Hospital from January 2018 to March 2022 were selected, and 153 healthy women with normal menstruation were selected as the control group. Fasting blood uric acid levels were measured by venous blood test, and body composition was measured by a body composition analyzer. Group comparisons were made to analyze the correlation between body composition and blood uric acid levels. Results: The incidence of hyperuricemia was higher in patients with PCOS than that in the control group [30.1% (46/153) vs 2.0% (3/153)], with a statistically significant difference (χ 2 =44.429, P <0.001). Blood uric acid level was also significantly higher in patients with PCOS than that in the control group [(371±98) vs (265±67) μmol/L; t =11.170, P <0.001]. Among PCOS patients, there were statistically significant differences in weight, body mass index (BMI), body fat mass, skeletal muscle mass, percent body fat, lean body weight, fat mass/lean body weight, percent skeletal muscle, and visceral fat level between the hyperuricemia group and the normal blood uric acid group (all P <0.001), but no significant difference was observed in waist-hip ratio ( P =0.348). The following body composition indicators: weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, visceral fat level, lean body weight, and fat mass/lean body weight in all subjects, the PCOS patients and the control group, were positively correlated with blood uric acid levels (all P <0.01). The blood uric acid level in PCOS obese patients was higher than that in non-obese PCOS patients, and the difference was statistically significant [(425±83) vs (336±91) μmol/L; t =6.133, P <0.001]. The blood uric acid level in central obesity PCOS patients was also higher than that in non-central obesity PCOS patients [(385±95) vs (299±79) μmol/L], the difference was statistically significant ( t =4.261, P <0.001). The blood uric acid level in normal-weight obese PCOS patients was higher than that in normal-weight non-obese PCOS patients [(333±73) vs (277±54) μmol/L], and the difference was statistically significant ( t =2.848, P =0.006). Blood uric acid levels in normal-weight [(315±74) vs (255±67) μmol/L], overweight [(362±102) vs (276±57) μmol/L], and obese PCOS patients [(425±83) vs (303±74) μmol/L] were all higher than those in the corresponding control groups, with statistically significant differences (all P <0.001). Conclusions: PCOS patients have a higher incidence of hyperuricemia than healthy women of childbearing age. Blood uric acid levels are closely correlated with body composition indicators, such as weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, and visceral fat level. Body composition analysis of women with PCOS could help identify potentially obese people more accurately and carry out individualized treatment, thereby reducing the risk of metabolic abnormalities.

Seed germination is a complex process that is regulated by various exogenous and endogenous factors, in which abscisic acid (ABA) plays a crucial role. The triphosphate tunnel metalloenzyme (TTM) superfamily exists in all living organisms, but research on its biological role is limited. Here, we reveal that TTM2 functions in ABA-mediated seed germination. Our study indicates that TTM2 expression is enhanced but repressed by ABA during seed germination. Promoted TTM2 expression in 35S::TTM2-FLAG rescues ABA-mediated inhibition of seed germination and early seedling development and ttm2 mutants exhibit lower seed germination rate and reduced cotyledon greening compared with the wild type, revealing that the repression of TTM2 expression is required for ABA-mediated inhibition of seed germination and early seedling development. Further, ABA inhibits TTM2 expression by ABA insensitive 4 (ABI4) binding of TTM2 promoter and the ABA-insensitive phenotype of abi4-1 with higher TTM2 expression can be rescued by mutation of TTM2 in abi4-1 ttm2-1 mutant, indicating that TTM2 acts downstream of ABI4 . In addition, TTM1 , a homolog of TTM2 , is not involved in ABA-mediated regulation of seed germination. In summary, our findings reveal that TTM2 acts as a downstream factor of ABI4 in ABA-mediated seed germination and early seedling growth.

High salinity, an adverse environmental factor affecting about 20% of irrigated arable land worldwide, inhibits plant growth and development by causing oxidative stress, damaging cellular components, and disturbing global metabolism. However, whether and how reactive oxygen species disturb the metabolism of salt-stressed plants remain elusive. Here, we report that salt-induced hydrogen peroxide (H2O2) inhibits the activity of plastid triose phosphate isomerase (pdTPI) to promote methylglyoxal (MG) accumulation and stimulates the sulfenylation of pdTPI at cysteine 74. We also show that MG is a key factor limiting the plant growth, as a decrease in MG levels completely rescued the stunted growth and repressed salt stress tolerance of the pdtpi mutant. Furthermore, targeting CATALASE 2 into chloroplasts to prevent salt-induced overaccumulation of H2O2 conferred salt stress tolerance, revealing a role for chloroplastic H2O2 in salt-caused plant damage. In addition, we demonstrate that the H2O2-mediated accumulation of MG in turn induces H2O2 production, thus forming a regulatory loop that further inhibits the pdTPI activity in salt-stressed plants. Our findings, therefore, illustrate how salt stress induces MG production to inhibit the plant growth., Competing Interests: Conflict of interest statement. The authors declare no conflict of interests., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Arabidopsis H3K9 methyltransferases KRYPTONITE/SUPPRESSOR OF VARIEGATION 3-9 HOMOLOG 4 (KYP/SUVH4), SUVH5 and SUVH6 are redundantly involved in silencing of transposable elements (TEs). Our recent study indicated that KYP/SUVH5/6 can directly interact with the histone deacetylase HDA6 to synergistically regulate TE expression. However, the function of KYP/SUVH5/6 in plant development is still unclear. The transcriptional factors ASYMMETRIC LEAVES1 (AS1) and AS2 form a transcription complex, which is involved in leaf development by repressing the homeobox genes KNOTTED-LIKE FROM ARABIDOPSIS THALIANA 1 (KNAT1) and KNAT2. In this study, we found that KYP and SUVH5/6 directly interact with AS1-AS2 to repress KNAT1 and KNAT2 by altering histone H3 acetylation and H3K9 dimethylation levels. In addition, KYP can directly target the promoters of KNAT1 and KNAT2, and the binding of KYP depends on AS1. Furthermore, the genome-wide occupancy profile of KYP indicated that KYP is enriched in the promoter regions of coding genes, and the binding of KYP is positively correlated with that of AS1 and HDA6. Together, these results indicate that Arabidopsis H3K9 methyltransferases KYP/SUVH5/6 are involved in leaf development by interacting with AS1-AS2 to alter histone H3 acetylation and H3K9 dimethylation from KNAT1 and KNAT2 loci., (© 2023. The Author(s).)

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 ( OR =0.41, 95% CI: 0.21-0.79, P =0.008), rs579408( OR =1.54, 95% CI: 1.03-2.29, P =0.034) and rs543923 ( OR =0.63, 95% CI: 0.41-0.98, P =0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 ( OR =0.55, 95% CI: 0.33-0.91, P =0.020) and GSDME rs2954558 ( OR =1.52, 95% CI: 1.01-2.31, P =0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 ( OR =0.36, 95% CI: 0.16-0.83, P =0.017), GSDME rs12540919 ( OR =0.52, 95% CI: 0.27-0.99, P =0.045) and NLRP3 rs3806268 ( OR =1.51, 95% CI: 1.03-2.22, P =0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P >0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P <0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

The cAMP response element binding protein 1 (CREB1) is an important nuclear transcription factor in eukaryotes. To explore the potential role of CREB1 on Qinchuan bovine skeletal myoblasts, we investigated the function of CREB1 on proliferation and differentiation. In this study, we found that CREB1 promoted cell proliferation by promoting DNA synthesis in S phase and cell division in G2 phase and promoted myogenic differentiation process in bovine myoblasts. Through dual luciferase experiments, we found that CREB1 can bind to the proximal promoter regions of CCNA2 and MyoG, indicating that CREB1 can play a positive regulatory role in the proliferation and differentiation of myoblasts by mediating the transcription of CCNA2 and MyoG. In addition, through downstream target gene analysis and transcriptome sequencing, we found that CREB1 plays a role in cell proliferation, myogenic differentiation, skeletal muscle repair and other related pathways., (Copyright © 2022. Published by Elsevier B.V.)

Arabidopsis (Arabidopsis thaliana) FLOWERING LOCUS C (FLC) acts as a key flowering regulator by repressing the expression of the floral integrator FLOWERING LOCUS T (FT). Prolonged exposure to cold (vernalization) induces flowering by reducing FLC expression. The long noncoding RNAs (lncRNAs) COOLAIR and COLDAIR, which are transcribed from the 3' end and the first intron of FLC, respectively, are important for FLC repression under vernalization. However, the molecular mechanism of how COOLAIR and COLDAIR are transcriptionally activated remains elusive. In this study, we found that the group-III WRKY transcription factor WRKY63 can directly activate FLC. wrky63 mutant plants display an early flowering phenotype and are insensitive to vernalization. Interestingly, we found that WRKY63 can activate the expression of COOLAIR and COLDAIR by binding to their promoters.WRKY63 therefore acts as a dual regulator that activates FLC directly under non-vernalization conditions but represses FLC indirectly during vernalization through inducing COOLAIR and COLDAIR. Furthermore, genome-wide occupancy profile analyses indicated that the binding of WRKY63 to vernalization-induced genes increases after vernalization. In addition, WRKY63 binding is associated with decreased levels of the repressive marker Histone H3 Lysine 27 trimethylation (H3K27me3). Collectively, our results indicate that WRKY63 is an important flowering regulator involved in vernalization-induced transcriptional regulation., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

To determine whether glutamine consumption is associated with embryo quality and aneuploidy, a retrospective study was conducted in an in vitro fertilization center. Spent embryo culture media from patients undergoing assisted reproduction treatment and preimplantation genetic testing (PGT) were obtained on day 3 of in vitro culture. Embryo quality was assessed for cell number and fragmentation rate. PGT for aneuploidy was performed using whole genome amplification and DNA sequencing. Glutamine levels in spent embryo culture media were analyzed by gas chromatography-mass spectrometry. The results demonstrated that glutamine was a primary contributor to the classification of the good-quality and poor-quality embryos based on the orthogonal partial least-squares discriminant analysis model. Glutamine consumption in the poor-quality embryos was significantly higher than that in the good-quality embryos (P < 0.05). A significant increase in glutamine consumption was observed from aneuploid embryos compared with that from euploid embryos (P < 0.01). The Pearson correlation coefficients between embryo quality and glutamine consumption, and between aneuploidy and glutamine consumption, were 0.430 and 0.757, respectively. The area under the ROC curve was 0.938 (95% CI: 0.902-0.975) for identifying aneuploidy. Animal experiments demonstrate that increased glutamine consumption may be a compensatory mechanism to mitigate oxidative stress. Our data suggest that glutamine consumption is associated with embryo quality and aneuploidy. Glutamine may serve as a molecular indicator for embryo assessment and aneuploidy testing., (© 2022. The Author(s).)

Objective: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) on apoptosis of intestinal T lymphocytes, translocation of intestinal bacteria and expression of intestinal Bcl-2 and Bax proteins and intestinal mucosal immune barrier in sepsis rats, so as to explore its underlying mechanism in relieving sepsis., Methods: SD rats were randomly divided into sham operation ( n =6), model ( n =15), non-meridian and non-acupoint (non-acupoint, n =15) and acupoint EA( n =15) groups by using random number table method. The sepsis model was established by using cecal ligation and perforation(CLP) method. EA (2 Hz, 2 mA) was applied to bilateral ST36 or non-acupoint for 30 min one hour after modeling, once every day for 3 days. The rats' general conditions and fatality rate in 3 days after modeling were recorded. The liver, spleen and mesenteric lymph nodes were taken for bacterial culture to detect the translocation rate of intestinal bacteria. The small intestinal tissue was taken for observing histopathological changes (Chiu's score: 0-5 points) after HE staining, and for determining the expression levels of Bcl-2 and Bax proteins using Western blot. The intestinal mucosa was sampled for detecting the apop-tosis (apoptotic index) of lymphocytes by using terminal deoxynucleoitidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) assay, and the counts of CD4+ and CD8+T cells using flow cytometry. The contents of IL-4 in the small intestine and that of secretory IgA (sIgA) in the small intestinal mucus were determined by using ELISA., Results: After modeling, of the 15 rats in each of the 3 groups, 7, 7 and 2 in the model, non-acupoint and EA groups were dead in the first 3 days, with the fatality rate being 46.67% (7/15), 46.67% (7/15) and 13.33% (2/15), respectively (being obviously lower in the EA group than in the former two groups, P <0.05). Compared with the sham operation group, the incidence of intestinal bacterial translocation, apoptotic index, Chiu's score, and Bax expression were significantly increased ( P <0.05), and the percentages of CD4 + and CD8 + T cells, IL-4 and sIgA contents and Bcl-2 expression considerably decreased ( P <0.05) in the model group. In comparison with the model group, modeling-induced increase of incidence of bacterial translocation, apoptotic index and Bax expression, and decrease of percentages of CD4 + and CD8 + T cells, IL-4 and sIgA contents and Bcl-2 expression were reversed ( P <0.05) in the EA group., Conclusion: EA at ST36 can reduce death rate and intestinal bacteria translocation incidence in sepsis rats, which may be related to its functions in regulating the expression of intestinal Bcl-2 and Bax proteins and inhibiting the apoptosis of intestinal mucosal T lymphocytes, thereby protecting the immune barrier function of intestinal mucosa to reduce the intestinal permeability.

Background: Some patients with knee osteoarthritis (KOA) show pain, stiffness and limited flexion and extension at the back of the knee, leading to dysfunction and affecting life. This may be related to changes in the biomechanical properties of skeletal muscles. Shear wave elastography (SWE) can detect these changes by measuring muscle shear modulus., Aims: To investigate hamstring muscle shear modulus of healthy people and patients was studied using SWE method, and the correlation analysis between the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of patients' subjective feeling and shear modulus of objective quantification was conducted., Methods: The hamstring shear modulus was measured by SWE in 50 patients and 50 healthy individuals. Pearson correlation coefficient was used to evaluate the correlation between hamstring stiffness and shear modulus in patients., Results: The hamstring shear modulus were significantly higher in the KOA group [the semimembranosus (SM) 15.23 ± 7.23, the semitendinosus (ST) 15.94 ± 5.40, the biceps femoris long tendinitis (BFL) 14.21 ± 6.55] than in the control group (the SM 10.95 ± 2.41, the ST 11.25 ± 2.23, the BFL 9.98 ± 2.81) ( p = 0.000, p = 0.000, p = 0.001). The hamstring shear modulus in the KOA group was moderately positively correlated with pain, shear modulus, and physical function score., Conclusion: Preliminary results show that the shear modulus of the hamstring of KOA patients is higher than that of healthy people, the WOMAC score and the shear modulus of patients are moderately correlated. These preliminary results show that ultrasonic shear wave elastography measurement of shear modulus may be enough to sensitive, can detect these effects, more targeted in order to assist the doctor's diagnosis and treatment., 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, Wang, Zhang, Shen, Guo, Guo, Feng, Zhang, Wen, Zhang, Fan and Fan.)

Importance: Several studies have explored the efficacy and toxic effects of concurrent 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) with or without oxaliplatin in the neoadjuvant setting. Addition of oxaliplatin to 5-FU or capecitabine elicited similar outcomes but with significantly increased toxic effects; however, there is a need for randomized clinical trials comparing 2 CRT regimens for patients receiving CRT in the adjuvant setting., Objective: To explore the efficacy and toxic effects of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy (RT) for pathological stage II and III rectal cancer., Design, Setting, and Participants: This multicenter randomized clinical trial enrolled patients from 7 centers in China between April 1, 2008, and December 30, 2015. Patients with pathologically confirmed stage II and III rectal cancer were randomized (1:1) to receive concurrent CRT with capecitabine or capecitabine plus oxaliplatin. Analysis was conducted from December 31, 2019, to March 15, 2020., Interventions: RT comprised 45 to 50 Gy in 25 fractions of 1.8 to 2.0 Gy over 5 weeks. In the capecitabine with RT group, concurrent chemotherapy included 2 cycles of capecitabine (1600 mg/m2) on days 1 to 14 and 22 to 35. The capecitabine and oxaliplatin with RT group received identical postoperative RT to that in the capecitabine with RT group combined with capecitabine (1300 mg/m2) on days 1 to 14 and 22 to 35 and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Patients in both groups received adjuvant chemotherapy (capecitabine or fluorouracil and oxaliplatin) after CRT., Main Outcomes and Measures: The primary end point was 3-year disease-free survival (DFS)., Results: A total of 589 patients (median [IQR] age, 55 [47-52] years; 375 [63.7%] men and 214 [36.3%] women) were enrolled, including 294 patients randomized to the capecitabine with RT group and 295 patients randomized to the capecitabine and oxaliplatin with RT group. Median (IQR) follow-up was 68 (45-96) months. Most patients had stage III disease (574 patients [75.9%]). Three-year DFS was 76.3% for the capecitabine with RT group and 74.1% for the capecitabine and oxaliplatin with RT group, and 5-year DFS was 72.0% for the capecitabine with RT group and 71.1% for the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P = .68). There was no significant difference between groups in overall survival (HR, 0.93; 95% CI, 0.64-1.34; P = .70) or local recurrence (HR, 0.61; 95% CI, 0.31-1.22; P = .16). More grade 3 and 4 acute toxic effects were observed in the capecitabine and oxaliplatin with RT group than in the capecitabine with RT group (114 patients [38.6%] vs 84 patients [28.6%]; P = .01)., Conclusions and Relevance: This randomized clinical trial found that addition of oxaliplatin to capecitabine-based postoperative CRT did not improve the efficacy of treatment but increased the risk of severe acute toxic effects. This finding highlights the basic role of postoperative capecitabine with RT for patients with locally advanced rectal cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT00714077.

Introduction: This study investigated the separate impact of first eye and second eye cataract surgery on driving performance, as measured on a driving simulator., Method: Forty-four older drivers with bilateral cataract aged 55+ years, awaiting first eye cataract surgery participated in a prospective cohort study. They completed a questionnaire, visual tests and a driving simulator assessment at three time points: before first eye, after first eye, and after second eye cataract surgery. Generalized Estimating Equation Poisson or linear regression models were undertaken to examine the change in four driving outcomes of interest after adjusting for cataract surgery and other potential confounders., Results: The rate of crashes/near crashes decreased significantly by 36% (incidence rate ratio (IRR) 0.64, 95% CI 0.47-0.88, p = 0.01) after first eye surgery and 47% (IRR 0.53, 95% CI 0.35-0.78, p < 0.001) after second eye surgery, compared to before first eye cataract surgery, after accounting for confounders. The rate of crashes/near crashes also decreased with better contrast sensitivity (IRR 0.69, 95% CI 0.48-0.90, p = 0.041). A separate model found that time spent speeding 10 kilometers per hour or more over the limit after second eye surgery was significantly less (0.14 min, p = 0.002), compared to before first eye surgery, after accounting for confounders. As contrast sensitivity improved, the duration of speeding also decreased significantly by 0.46 min (p = 0.038). There were no statistically significant changes in lane excursions or speed variation. Practical applications: The findings highlight the importance of timely first and second eye cataract surgery to ensure driver safety, especially as older drivers wait for second eye cataract surgery. It also provides further evidence that contrast sensitivity is probably a better predictor of driving ability in older drivers with cataract than visual acuity, the measure on which driver licensing requirements are currently based, and should also be used when assessing fitness to drive., (Copyright © 2021 National Safety Council and Elsevier Ltd. All rights reserved.)

Background: Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality. To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is reported to protect the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates radiation-induced intestinal injury., Aim: To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R., Methods: Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion. Intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells were challenged by hypoxia/ reoxygenation to mimic I/R in vitro ., Results: Indicators including fluorescein isothiocyanate-conjugated dextran (4 kilodaltons; FD-4) clearance, ratio of phosphorylated myosin light chain/total myosin light chain, myosin light chain kinase and loss of zonula occludens-1, claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation. rhANGPTL4 treatment significantly reversed these indicators, which were associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and improvement of survival rate. Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation, whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly., Conclusion: rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Arabidopsis thaliana CONSTANS (CO) is an essential transcription factor that promotes flowering by activating the expression of the floral integrator FLOWERING LOCUS T (FT). A number of histone modification enzymes involved in the regulation of flowering have been identified, but the involvement of epigenetic mechanisms in the regulation of the core flowering regulator CO remains unclear. Previous studies have indicated that the transcription factors, FLOWERING BHLH1 (FBH1), FBH2, FBH3, and FBH4, function redundantly to activate the expression of CO. In this study, we found that the KDM3 group H3K9 demethylase JMJ28 interacts with the FBH transcription factors to activate CO by removing the repressive mark H3K9me2. The occupancy of JMJ28 on the CO locus is decreased in the fbh quadruple mutant, suggesting that the binding of JMJ28 is dependent on FBHs. Furthermore, genome-wide occupancy profile analyses indicate that the binding of JMJ28 to the genome overlaps with that of FBH3, indicating a functional association of JMJ28 and FBH3. Together, these results indicate that Arabidopsis JMJ28 functions as a CO activator by interacting with the FBH transcription factors to remove H3K9me2 from the CO locus., (� American Society of Plant Biologists 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The aim of the study is to compare driving exposure, patterns and factors associated with safety critical events between drivers with MCI and a comparison group without cognitive impairment., Design, Setting, Participants: Naturalistic driving data using an in-vehicle monitoring device were collected from 36 older drivers with MCI and 35 older drivers without cognitive impairment over a two-week period in Western Australia., Measurements: Naturalistic driving exposure, patterns (eg. night-time trips, peak-hour trips) and safety critical events (harsh acceleration, harsh braking and harsh cornering)., Results: Drivers with MCI had a lower number of safety critical events (mean = 7.20, SD = 11.44) compared to drivers without cognitive impairment (mean = 10.89, SD = 23.30) however, this was not statistically significantly. There were also no statistically significant differences between drivers with and without MCI for measures of driving exposure or any of the driving patterns including weekday trips, night-time trips and trips on highways/freeways. The results of the multivariable modelling found only binocular contrast sensitivity was associated with the rate of safety critical events. For every increase of 0.1 log units in contrast sensitivity (better contrast sensitivity) the rate of safety critical events significantly decreased by 30 % (IRR = 0.70, 95 % CI = 0.50-0.98, p = 0.04)., Conclusion: Drivers with MCI were found to have similar driving exposure and patterns compared to older drivers without cognitive impairment, however drivers with better contrast sensitivity experienced fewer safety critical events. Future research should consider a longitudinal study design with an extended driving monitoring period and a larger sample with a clinical diagnosis of MCI to assess changes in cognition and its impact on driving., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Methylglyoxal (MG) is a byproduct of glycolysis that functions in diverse mammalian developmental processes and diseases and in plant responses to various stresses, including salt stress. However, it is unknown whether MG-regulated gene expression is associated with an epigenetic modification. Here we report that MG methylglyoxalates H3 including H3K4 and increases chromatin accessibility, consistent with the result that H3 methylglyoxalation positively correlates with gene expression. Salt stress also increases H3 methylglyoxalation at salt stress responsive genes correlated to their higher expression. Following exposure to salt stress, salt stress responsive genes were expressed at higher levels in the Arabidopsis glyI2 mutant than in wild-type plants, but at lower levels in 35S::GLYI2 35S::GLYII4 plants, consistent with the higher and lower MG accumulation and H3 methylglyoxalation of target genes in glyI2 and 35S::GLYI2 35S::GLYII4, respectively. Further, ABI3 and MYC2, regulators of salt stress responsive genes, affect the distribution of H3 methylglyoxalation at salt stress responsive genes. Thus, MG functions as a histone-modifying group associated with gene expression that links glucose metabolism and epigenetic regulation., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Plant trichomes are large single cells that are organized in a regular pattern and play multiple biological functions. In Arabidopsis, trichome development is mainly governed by the core trichome initiation regulators, including the R2R3 type MYB transcript factor GLABRA 1 (GL1), bHLH transcript factors GLABRA 3/ENHANCER OF GLABRA 3 (GL3/EGL3), and the WD-40 repeat protein TRANSPARENT TESTA GLABRA 1 (TTG1), as well as the downstream trichome regulator GLABRA 2 (GL2). GL1, GL3/EGL3, and TTG1 can form a trimeric activation complex to activate GL2, which is required for the trichome initiation and maintenance during cell differentiation. Arabidopsis JMJ29 is a JmjC domain-containing histone demethylase belonging to the JHDM2/KDM3 group. Members of the JHDM2/KDM3 group histone demethylases are mainly responsible for the H3K9me1/2 demethylation. In the present study, we found that the trichome density on leaves and inflorescence stems is significantly decreased in jmj29 mutants. The expression of the core trichome regulators GL1, GL2, and GL3 is decreased in jmj29 mutants as well. Furthermore, JMJ29 can directly target GL3 and remove H3K9me2 on the GL3 locus. Collectively, we found that Arabidopsis JMJ29 is involved in trichome development by directly regulating GL3 expression. These results provide further insights into the molecular mechanism of epigenetic regulation in Arabidopsis trichome development., (© 2020 Society for Experimental Biology and John Wiley & Sons Ltd.)

Objective: To investigate the associations between the genetic variations of apoptosis genes and the adverse events of postoperative concurrent chemoradiotherapy in patients with rectal cancer. Methods: We enrolled 362 patients with stage Ⅱ to Ⅲ rectal cancer who received concurrent chemoradiotherapy. Whole blood sample (2 ml) was collected from patient at the time of enrollment before therapy. Sequenom MassARRAY was used to detect the genotypes of 29 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight apoptosis genes, including Fas cell surface death receptor(FAS), Fas ligand(FASL), apoptotic peptidase activating factor 1(APAF1), BCL2 associated X(BAX), TNF-related apoptosis-inducing ligand(TRAIL), TNF-related apoptosis-inducing ligand receptor 1(TRAILR1), TNF-related apoptosis-inducing ligand receptor 2(TRAILR2) and caspase-7(CASP7). The associations between genotypes and adverse events of chemoradiotherapy were measured by unconditional logistic regression model. Results: Three hundred and sixty two patients were treated with total mesorectal excision surgery followed by a total radiation dose of 50 Gy applied in 25 fractions over a period of 5 weeks concurrently with daily administration of capecitabine (1 600 mg/m(2) per day, continuously for 2 weeks and taking a week off every 21-day cycle). One hundred and six patients (29.3%) had grade≥2 myelosuppression. Three SNPs associated with the risk of grade ≥2 myelosuppression included FAS rs1468063 ( OR =1.51, 95% CI: 1.07-2.15, P =0.020), APAF1 rs11296996 ( OR =0.69, 95% CI: 0.49-0.98, P =0.039) and BAX rs4645904 ( OR =0.69, 95% CI: 0.50-0.97, P =0.030). One hundred and sixty one patients (44.5%) developed grade≥2 diarrhea. Five SNPs that significantly associated with risk of grade≥2 diarrhea included APAF1 rs11296996 ( OR =1.42, 95% CI: 1.02-2.00, P =0.040), rs74619561 ( OR =2.16, 95% CI: 1.27-3.68, P =0.005), CASP7 rs12263370 ( OR =1.67, 95% CI: 1.05-2.66, P =0.029), rs12247479 ( OR =1.85, 95% CI: 1.12-3.08, P =0.017) and TRAIL rs112822654 ( OR =0.68, 95% CI: 0.48-0.96, P =0.027). The remaining SNPs were not related to the adverse events of chemoradiotherapy (all P >0.05). Grade≥2 myelosuppression occurred less frequently in male than in female ( P =0.046); Surgical treatment and tumor location had great impact on the occurrence of grade≥2 diarrhea (all P <0.001) and dermatitis (all P <0.05). Conclusions: The genetic variations of FAS, APAF1, BAX, TRAIL and CASP7 are related to the adverse events of concurrent chemoradiotherapy in patients with rectal cancer, which may be potential genetic biomarkers for individualized treatment of rectal cancer.

Exploring efficient and stable oxygen evolution reaction (OER) catalysts with earth-abundant elements has been an urgent task in water splitting. Metal-organic frameworks (MOFs), possessing abundant active metal sites and tunable porous crystalline structures, are promising as OER catalysts. In this paper, a MOF based on benzotriazole-5-carboxylate (Co3-btca) that contains unsaturated coordinated metal centers and a 1D channel was selected to act as an OER catalyst. To optimize the OER performance, isostructural bimetallic and trimetallic frameworks were obtained by doping with Fe and/or Ni ions. The optimized Co2.36Fe0.19Ni0.45-btca possesses the lowest overpotential of 292 mV at 10 mA cm-2 and a small Tafel slope of 72.6 mV dec-1. The enhanced catalytic performance could be attributed to the synergistic effect between the unsaturated coordinated Co, Fe and Ni sites, which are beneficial for the nucleophilic attack of OH- forming adsorption intermediates.

Higenamine (HG), a cardioactive component of some foods and medicines, has been listed in the doping category by the International Olympic Committee, which may lead to misuse by athletes. We report the development of a gas chromatography-mass spectrometry (GC-MS) method for determination of HG in various matrix samples (biological samples, different forms of Chinese patent medicine, Chinese herbal medicine) based on acylation derivatization of HG by heptafluorobutyric anhydride. Under optimal conditions, the linearity of HG in the range of 5-200 ng mL -1 was acceptable (R 2  > 0.999), and the limit of detection (LOD) and limit of quantitation (LOQ) for HG was 1.52 ng mL -1 and 5 ng mL -1 , respectively. Low, medium, and high concentrations (25, 100 and 160 ng mL -1 ) of HG were added to plasma, urine, oral liquid, capsule, watered bolus, honeyed bolus and Chinese herbal medicine samples, with recovery ranging from 82.70 to 109.80%, intra-day and inter-day precisions were both less than 3.39%. The results indicated that the method had sufficient sensitivity for analysis of biological samples, and Chinese patent and herbal medicine., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Sensitization with dyes is the most promising option to narrow the band gap and improve visible-light absorption of TiO 2 . As ideal structure and reaction models of TiO 2 , titanium oxo clusters (TOCs) with exact crystal structure are beneficial for further understanding the structure-property relationship of TiO 2 . Most reports mainly focus on the synthesis and properties of TOCs, but research on the band-gap tuning of TOCs at the large range of 3.7-2.0 eV by chromophore ligands (CLs) has been lacking. Herein, six new Ti 6 -core-based TOCs (Ti 6 -TOCs) were successfully synthesized by using CLs in a simple and general approach. Each Ti 6 -TOC structure contains two Ti 3 (μ 3 -O) units featuring a flat or pyramidal mode as building blocks. Five Ti 6 -core structure types were present among the six Ti 6 -TOCs, which enriched the family of hexanuclear TOCs. To be noted, the band-gap values were tuned at a wide range of 3.41-1.98 eV by controlling the type and number of the CLs 2-hydroxypyridine, salicylaldoxime, and catechol in the structure. Density functional theory calculation revealed that the lowest-energy bands of these Ti 6 -TOCs are attributed to the CL-to-TiO core charge-transfer bands. This work provides a precise and wide-ranged band-gap tuning method for TOCs. Additionally, the six Ti 6 -TOCs exhibit good photocurrent response.

Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.

Silver doped TiO 2 (Ag-TiO 2 ) materials show high activity and good stability in photocatalysis, but the mechanism could not be illustrated clearly due to their imprecise and inhomogeneous characteristics. Ag-doped titanium-oxo clusters (Ag-TOCs) with an exact crystal structure, which are rarely reported, are beneficial for further understanding structure-property relationships. Herein, six new Ag-TOCs with a butterfly-like Ti 8 Ag 2 core have been synthesized through facile solvothermal reactions, in which two Ag ions are successfully linked to the surface of the Ti 8 core. Of interest, the Ti 6 unit of the Ti 8 Ag 2 core is similar to that found in the anatase structure and may be a promising model for Ag-TiO 2 materials. The band gaps of these Ag-TOCs show different values mainly affected by different ligands. DFT calculations revealed that the lowest energy bands of Ag-TOCs are attributed to the Ag-to-TiO core charge transfer bands. Additionally, all Ag-TOCs exhibit good photoelectric response and high photodegradation activity towards organic dyes.

DNA methylation is a chromatin mark that has a crucial role in regulating gene expression. The chromomethylase (CMT) protein family is a plant-specific DNA methyltransferase that mediates growth and development. However, the roles of CMT3 in autophagy remain to be elucidated. Here, we identified the potential targets of CMT3 in Nicotiana benthamiana (NbCMT3) during developmental programs. Virus-induced gene silencing of NbCMT3/3-2 in N. benthamiana had pleiotropic effects on plant morphology, which indicates its indispensible role in development. Genome-wide transcriptome analysis of NbCMT3/3-2-silenced plants revealed interference with genes related to autophagy and ubiquitination. The expression of NbBeclin 1 and NbHRD1B was higher in NbCMT3/3-2-silenced than control plants. The formation of autophagosomes and starch degradation was disrupted in NbCMT3/3-2-silenced plants, which implies a perturbed autophagic processes. We further generated transgenic N. benthamiana plants carrying a chimeric promoter-reporter construct linking the NbBeclin 1 promoter region and β-glucuronidase (GUS) reporter (pNbBeclin::GUS). NbBeclin 1 promoter activity was significantly enhanced in NbCMT3/3-2-silenced plants. Thus, NbCMT3/3-2 silencing had pleiotropic effects on development by interfering with NbBeclin 1 expression and autophagy-related processes., (� The Author(s) 2019. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the impact of first eye and second eye cataract surgery on the level of physical activity undertaken by older adults with bilateral cataract., Design: Prospective cohort study., Setting: Three public ophthalmology clinics in Western Australia., Participants: Fifty-five older adults with bilateral cataract aged 55+ years, awaiting first eye cataract surgery., Outcome Measures: The primary outcome measure was participation in moderate leisure-time physical activity. The secondary outcomes were participation in walking, gardening and vigorous leisure-time physical activity. Participants completed a researcher-administered questionnaire, containing the Active Australia Survey and visual tests before first eye cataract surgery, after first eye surgery and after second eye surgery. A Generalised Estimating Equation linear regression model was undertaken to analyse the change in moderate leisure-time physical activity participation before first eye surgery, after first eye surgery and after second eye surgery, after accounting for relevant confounders., Results: Participants spent significantly less time per week (20 min) on moderate leisure-time physical activity before first eye cataract surgery compared with after first eye surgery (p=0.04) after accounting for confounders. After second eye cataract surgery, participants spent significantly more time per week (32 min) on moderate physical activity compared with after first eye surgery (p=0.02). There were no significant changes in walking, gardening and vigorous physical activity throughout the cataract surgery process., Conclusion: First and second eye cataract surgery each independently increased participation in moderate leisure-time physical activity. This provides a rationale for timely first and second eye cataract surgery for bilateral cataract patients, even when they have relatively good vision., 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.)

Objective: To investigate the associations between genetic variations in DNA mismatch repair genes and sensitivity as well as prognosis to preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods: Fourteen haplotype-tagging single nucleotide polymorphisms (htSNPs) of MLH1, MLH3 and MSH2 genes were genotyped by Sequenom MassARRAY method in 146 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. The associations between genotypes and response to capecitabine-based neoadjuvant chemoradiotherapy (nCRT) were measured by odds ratios ( ORs ) and 95% confidence intervals ( CIs ), adjusted for sex, age, clinical stages and karnofsky performance score (KPS) by unconditional logistic regression model. The survival analyses were performed by the hazard ratios ( HR s) and 95% CIs by Cox proportional regression model. Results: Among 146 cases, 64 patients were nCRT responders with a response rate of 43.8%. MLH3 rs175057 C>T and MSH2 rs13019654 G>T loci were associated with the sensitivity to preoperative chemoradiotherapy. Compared with the rs175057 CC genotype, the adjusted OR for patients with CT and TT genotypes was 0.42 (95% CI: 0.19-0.91; P =0.029). Moreover, for rs13019654, the adjusted OR for patients with the GT or TT genotypes was 0.49 (95% CI: 0.24-0.98; P =0.047) than those with GG genotype. The remaining 12 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs3771273, rs4608577, rs4952887, rs6544991, rs6544997, rs10188090 and rs10191478, were not significantly associated with therapeutic response to preoperative chemoradiotherapy. Meanwhile, MLH3 rs175057 C>T locus was also associated with longer overall survival time in locally advanced rectal cancer ( HR =0.44, 95% CI: 0.20-0.96, P =0.038), whereas MSH2 rs3771273 T>A, rs10188090 A>G and rs10191478 T>G loci were associated with shorter overall survival time ( HR =1.74, 95% CI: 1.06-2.84, P =0.028; HR =1.64, 95% CI: 1.01-2.66, P =0.046; HR =1.71, 95% CI: 1.01-2.91, P =0.047, respectively). The remaining 10 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs4608577, rs4952887, rs6544991, rs6544997 and rs13019654, were not significantly associated with prognosis. Conclusions: Genetic polymorphisms of MLH3 rs175057 and MSH2 rs13019654 loci can predict the nCRT response, while MLH3 rs175057 as well as MSH2 rs3771273, rs10188090 and rs10191478 may predict prognosis in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. Therefore, these SNPs could be used as potential genetic markers in the personalized therapy of rectal cancer.

Background: Hendra virus and Nipah virus are zoonotic viruses that have caused severe to fatal disease in livestock and human populations. The isolation of Cedar virus, a non-pathogenic virus species in the genus Henipavirus, closely-related to the highly pathogenic Hendra virus and Nipah virus offers an opportunity to investigate differences in pathogenesis and receptor tropism among these viruses., Methods: We constructed full-length cDNA clones of Cedar virus from synthetic oligonucleotides and rescued two replication-competent, recombinant Cedar virus variants: a recombinant wild-type Cedar virus and a recombinant Cedar virus that expresses a green fluorescent protein from an open reading frame inserted between the phosphoprotein and matrix genes. Replication kinetics of both viruses and stimulation of the interferon pathway were characterized in vitro. Cellular tropism for ephrin-B type ligands was qualitatively investigated by microscopy and quantitatively by a split-luciferase fusion assay., Results: Successful rescue of recombinant Cedar virus expressing a green fluorescent protein did not significantly affect virus replication compared to the recombinant wild-type Cedar virus. We demonstrated that recombinant Cedar virus stimulated the interferon pathway and utilized the established Hendra virus and Nipah virus receptor, ephrin-B2, but not ephrin-B3 to mediate virus entry. We further characterized virus-mediated membrane fusion kinetics of Cedar virus with the known henipavirus receptors ephrin-B2 and ephrin-B3., Conclusions: The recombinant Cedar virus platform may be utilized to characterize the determinants of pathogenesis across the henipaviruses, investigate their receptor tropisms, and identify novel pan-henipavirus antivirals. Moreover, these experiments can be conducted safely under BSL-2 conditions.

Background: In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence., Methods: In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m 2 ) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included., Results: Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036)., Conclusions: In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Objective: To investigate individualized therapeutic strategy for bilateral carotid body tumors. Methods: Clinical data of 16 patients with bilateral carotid body tumor treated from January 2003 to August 2016 were retrospectively studied. Of the 16 patients, 9 were males and 7 were females; 5 were sporadic and 11 were familial; 8 cases were observed, 1 cases was malignant and treated with chemotherapy, and 7 cases were treated with surgery. The treatment course, perioperative complications and clinical efficacy were assessed. Comprehensive evaluation of bilateral carotid body tumors was performed based on the size of bilateral tumor, clinical manifestations, genetic tests and other indicators. Individual treatment strategies included observation, surgery and observation, bilateral surgery, radiotherapy or chemotherapy. Surgical resection of carotid body tumor was unilateral in 3 cases and bilateral in 3 cases; removal of bilateral carotid body tumors plus unilateral jugular bulb in 1 case; and the internal carotid artery was reconstructed with autologous greater saphenous vein in 1 case. Results: All patients were followed up for 3 months to 12 years. There was no patient death during perioperative period. Superior laryngeal nerve injury occurred in 2 case. Baroreceptor failure syndrome occurred in one patient, but it gradually recoverd with medical treatments. Conlusion: It is important to identify whether bilateral carotid body tumors are hereditary and to make an individualized therapeutic strategy for each patient with bilateral carotid body tumors, focusing on the improvement in the quality of life of patient.

Purpose: The role of adjuvant chemoradiotherapy (ACRT) or adjuvant chemotherapy (ACT) in treating patients with locally advanced upper rectal cancer (URC) after total mesorectal excision (TME) surgery remains unclear. We developed a clinical nomogram and a recursive partitioning analysis (RPA)-based risk stratification system for predicting 5-year cancer-specific survival (CSS) to determine whether these individuals require ACRT or ACT., Materials and Methods: This retrospective analysis included 547 patients with primary URC. A nomogram was developed based on the Cox regression model. The performance of the model was assessed by concordance index (C-index) and calibration curve in internal validation with bootstrapping. RPA stratified patients into risk groups based on their tumor characteristics., Results: Five independent prognostic factors (age, preoperative increased carcinoembryonic antigen and carcinoma antigen 19-9, positive lymph node [PLN] number, tumor deposit [TD], pathological T classification) were identified and entered into the predictive nomogram. The bootstrap-corrected C-index was 0.757. RPA stratification of the three prognostic groups showed obviously different prognosis. Only the high-risk group (patients with PLN ≤ 6 and TD, or PLN > 6) benefited from ACRT plus ACT when compared with surgery followed by ACRT or ACT, and surgery alone (5-year CSS: 70.8% vs. 57.8% vs. 15.6%, P < 0.001)., Conclusions: Our nomogram predicts 5-year CSS after TME surgery for locally advanced rectal cancer and RPA-based stratification indicates that ACRT plus ACT post-surgery may be an important treatment plan with potentially ignificant survival advantages in high-risk URC. This may help to select candidates of adjuvant treatment in prospective studies.