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Purpose Glutathione S-transferase mu (GSTM) belongs to the group of phase II drug-metabolizing enzymes, and the GSTM1 genetic variant has been reported to have a potential association with the metabolism of immunosuppressive drug after renal transplantation. The effect of donor and recipient GSTMs genetic variants on tacrolimus (Tac) metabolism was the focus of our investigation in this study. Methods A total of 203 liver transplant patients were recruited for the study. In the training set (n = 110), twenty-one SNPs in five genes (GSTM1-5) were genotyped by the drug-metabolizing enzymes and transporter (DMET) microarray. CYP3A5 rs776746 and GSTM3 rs7483 were genotyped using a Mass ARRAY platform in the validating set (n = 93). Results Tac C/D ratios of donor GSTM3 rs7483 AA carriers were significantly lower than those with the G allele at weeks 1, 2, 3 and 4 after liver transplantation (LT). Multivariate analysis was conducted on the training set and validating set, donor and recipient CYP3A5 rs776746, donor GSTM3 rs7483 and total bilirubin were identified as independent predictors of Tac C/D ratios in the early period after LT. Combining CYP3A5 rs776746 and donor GSTM3 rs7483 genotypes, Tac C/D ratios were observed to be increasingly lower with increasing numbers of alleles associated with fast metabolism. Moreover, the risk of a supratherapeutic C0 (Tac > 15 ug/L) was significantly higher for poor metabolizers than the other groups at week 1 after LT. Conclusions There was a significant association between the donor GSTM3 rs7483 genetic variant and Tac metabolism in the early period after LT. Genotype classification might have a better predictive ability of the initial Tac doses.

Climate change and intensified human activities have disrupted the natural hydrological regime and rhythm of river-connected lakes, extending the dry season, increasing water loss, and exposing previously submerged lake floors. This exposure has led to significant sediment hardening, which directly impacts submerged macrophytes. However, strategies to mitigate the negative effects of hardened sediments and promote the growth and development of submerged macrophytes remain largely unexplored. In this study, we selected typical hardened sediment from Dongting Lake to investigate the response of different growth forms of submerged macrophytes to multiple sediment remediation measures (loosening and litter addition) using a mesocosm experiment. The results indicated that loosening alone uniformly benefited all submerged macrophytes by increasing total biomass, relative growth rate (RGR), and the root/shoot ratio. Additionally, loosening altered the root traits of submerged macrophytes, promoting maximum root length (MRL) while reducing average root diameter (ARD). Moreover, different submerged macrophytes exhibited species-specific responses to the combination of loosening and litter addition. Notably, the combination of loosening and adding Miscanthus lutarioriparius litter had an antagonistic effect on the growth of Potamogeton wrightii and Myriophyllum spicatum. The response of functional traits of submerged macrophytes with similar growth forms to the same treatment was consistent. Our findings suggest that future sediment remediation efforts should consider matching specific treatments with the growth forms of submerged macrophytes to achieve optimal outcomes.

Abstract Background Alternative polyadenylation (APA) is an important pattern of post-transcriptional regulation of genes widely existing in eukaryotes, involving plant physiological and pathological processes. However, there is a dearth of studies investigating the role of APA profile in rice leaf blight. Results In this study, we compared the APA profile of leaf blight-susceptible varieties (CT 9737-613P-M) and resistant varieties (NSIC RC154) following bacterial blight infection. Through gene enrichment analysis, we found that the genes of two varieties typically exhibited distal poly(A) (PA) sites that play different roles in two kinds of rice, indicating differential APA regulatory mechanisms. In this process, many disease-resistance genes displayed multiple transcripts via APA. Moreover, we also found five polyadenylation factors of similar expression patterns of rice, highlighting the critical roles of these five factors in rice response to leaf blight about PA locus diversity. Conclusion Notably, the present study provides the first dynamic changes of APA in rice in early response to biotic stresses and proposes a possible functional conjecture of APA in plant immune response, which lays the theoretical foundation for in-depth determination of the role of APA events in plant stress response and other life processes.

Abstract Introduction The purpose of our study was to differentiate uterine carcinosarcoma (UCS) from endometrioid adenocarcinoma (EAC) by the multiparametric magnetic resonance imaging (MRI) features. Methods We retrospectively evaluated clinical and MRI findings in 17 patients with UCS and 34 patients with EAC proven by histologically. The following clinical and pathological features were evaluated: post- or pre-menopausal, clinical presentation, invasion depth, FIGO stage, lymphaticmetastasis. The following MRI features were evaluated: tumor dimension, cystic degeneration or necrosis, hemorrhage, signal intensity (SI) on T2-weighted images (T2WI), relative SI of lesion to myometrium on T2WI, T1WI, DWI, ADCmax, ADCmin, ADCmean (RSI-T2, RSI-T1, RSI-DWI, RSI-ADCmax, RSI-ADCmin, RSI-ADCmean), ADCmax, ADCmin, ADCmean, the maximum, minimum and mean relative enhancement (RE) of lesion to myometrium on the arterial and venous phases (REAmax, REAmin, REAmean, REVmax, REVmin, REVmean). Receiver operating characteristic (ROC) analysis and the area under the curve (AUC) were used to evaluate prediction ability. Results The mean age of UCS was higher than EAC. UCS occurred more often in the postmenopausal patients. UCS and EAC did not significantly differ in depth of myometrial invasion, FIGO stage and lymphatic metastasis. The anterior-posterior and transverse dimensions were significantly larger in UCS than EAC. Cystic degeneration or necrosis and hemorrhage were more likely occurred in UCS. The SI of tumor on T2WI was more heterogeneous in UCS. The RSI-T2, ADCmax, ADCmean, RSI-ADCmax and RSI-ADCmean of UCS were significantly higher than EAC. The REAmax, REAmin, REAmean, REVmax, REVmin and REVmean of UCS were all higher than EAC. The AUCs were 0.72, 0.71, 0.86, 0.96, 0.89, 0.84, 0.73, 0.97, 0.88, 0.94, 0.91, 0.69 and 0.80 for the anterior-posterior dimension, transverse dimension, RSI-T2, ADCmax, ADCmean, RSI-ADCmax, RSI-ADCmean, REAmax, REAmin, REAmean, REVmax, REVmin and REVmean, respectively. The AUC was 0.997 of the combined of ADCmax, REAmax and REVmax. Our study showed that ADCmax threshold value of 789.05 (10–3mm2/s) can differentiate UCS from EAC with 100% sensitivity, 76.5% specificity, and 0.76 AUC, REAmax threshold value of 0.45 can differentiate UCS from EAC with 88.2% sensitivity, 100% specificity, and 0.88 AUC. Conclusion Multiparametric MRI features may be utilized as a biomarker to distinguish UCS from EAC.

Previous studies have demonstrated a bidirectional relationship between inflammation and depression. Activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes is closely related to the pathogenesis of various neurological diseases. In patients with major depressive disorder, NLRP3 inflammasome levels are significantly elevated. Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies. In this review, we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome. Moreover, we outlined various therapeutic strategies that target the NLRP3 inflammasome, including NLRP3 inflammatory pathway inhibitors, natural compounds, and other therapeutic compounds that have been shown to be effective in treating depression. Additionally, we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression. Currently, there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment. The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression. Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.

Abstract The pathology of depression is related to the imbalance of various neurotransmitters. The dorsal raphe nucleus (DRN), the main brain region producing 5-HT, is crucially involved in the pathophysiology of depression. It contains several neuron types, in which GABAergic neurons are activated by stimuli associated with negative experiences and 5-HT neurons are activated by reward signals. However, little is known about its underlying molecular mechanisms. Here, we found that p11, a multifunctional protein associated with depression, was down-regulated by chronic social defeat stress in 5-HTDRN neurons. Knockdown of p11 in DRN induced depression-like behaviors, while its overexpression in 5-HTDRN neurons alleviated depression-like behavior caused by chronic social defeat stress. Further, p11 regulates membrane trafficking of glutamate receptors in 5-HTDRN neurons, suggesting a possible molecular mechanism underlying the participation of p11 in the pathological process of depression. This may facilitate the understanding of the molecular and cellular basis of depression.

Abstract Antimicrobial peptides are promising alternatives to conventional antibiotics. Herein, we report a class of “tadpole-like” peptides consisting of an amphipathic α-helical head and an aromatic tail. A structure-activity relationship (SAR) study of “tadpole-like” temporin-SHf and its analogs revealed that increasing the number of aromatic residues in the tail, introducing Arg to the α-helical head and rearranging the peptide topology dramatically increased antimicrobial activity. Through progressive structural optimization, we obtained two peptides, HT2 and RI-HT2, which exhibited potent antimicrobial activity, no hemolytic activity and cytotoxicity, and no propensity to induce resistance. NMR and molecular dynamics simulations revealed that both peptides indeed adopted “tadpole-like” conformations. Fluorescence experiments and electron microscopy confirmed the membrane targeting mechanisms of the peptides. Our studies not only lead to the discovery of a series of ultrashort peptides with potent broad-spectrum antimicrobial activities, but also provide a new strategy for rational design of novel “tadpole-like” antimicrobial peptides.

Compared to common salt, low-sodium salt can reduce blood pressure to varying degrees. However, the exact dosage relationship remains unclear. We aimed to investigate the dose–response relationships between low-sodium salt intake and systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as the risk of hypertension, and to determine the optimal range for low-sodium salt intake. We investigated the basic characteristics and dietary profile of 350 individuals who consumed low-sodium salt. The samples were divided into three groups according to the 33.3rd and 66.6th percentiles of low-sodium salt intake in condiments (Q1:

Under-deposit corrosion is widely present in the pipelines of oil and gas production, causing significant corrosion damage. In this paper, a novel electrochemical cathodic-polarization method was carried out to accelerate the formation of CaCO3 scale on a X65 steel surface in a simulated solution containing scaling ions. Subsequently, pre-scaled X65 steel was placed in a high temperature and pressure autoclave to conduct corrosion weight-loss experiments and in situ electrochemical measurements. The study mainly compared the corrosion inhibition behavior of four quaternary ammonium salt corrosion inhibitors, pyridinium quaternary salt (BPC), quinolinium quaternary salt (BQC), 8-hydroxyquinolinium quaternary salt (BHQ) and pyridinium (1-chloromethyl naphthalene) quaternary salt (1-CPN), in a simulated oilfield scale under corrosive conditions. The results of the weight-loss experiments demonstrated that the inhibition efficiencies of the corrosion inhibitors from high to low were as follows: 1-CPN < BHQ < BQC < BPC. The in situ electrochemical measurements showed that the immersion time and type of corrosion inhibitor had a pronounced influence on the corrosion and corrosion inhibition behavior of X65 steel with CaCO3 coating. It was also proved using both EIS and PC that 1-CPN shows the best inhibition performance in all. Lastly, the inhibition mechanism of corrosion inhibitors at under-deposit conditions was analyzed via a surface morphology observation of SEM.

Pancreatic β-cell failure is a pathological feature in type 1 diabetes. One promising approach involves inducing transdifferentiation of related pancreatic cell types, specifically α cells that produce glucagon. The chemokine stromal cell-derived factor-1 alpha (SDF-1α) is implicated in pancreatic α-to-β like cell transition. Here, the serum level of SDF-1α was lower in T1D with C-peptide loss, the miR-23a was negatively correlated with SDF-1α. We discovered that exosomal miR-23a, secreted from β cells, functionally downregulates the expression of SDF-1α, leading to increased Pax4 expression and decreased Arx expression in vivo. Adenovirus-vectored miR-23a sponge and mimic were constructed to further explored the miR-23a on pancreatic α-to-β like cell transition in vitro, which yielded results consistent with our cell-based assays. Suppression of miR-23a upregulated insulin level and downregulated glucagon level in STZ-induced diabetes mice models, effectively promoting α-to-β like cell transition. Our findings highlight miR-23a as a new therapeutic target for regenerating pancreatic β cells from α cells.

Major depressive disorder (MDD) is a disabling and severe psychiatric disorder with high risk of suicide, and adulthood is one of the most probable period for the onset. The neural basis underlying the young adults with MDD remains underexplored. In this study, we have investigated the cortical and subcortical alterations of neuroanatomical structures and functional activation in twenty-three young depressive patients with suicide attempt versus forty-five healthy controls. Significant disruptions of regional gray matter volume at left middle frontal extending to superior frontal involved with cognitive processing were found correlated with anxiety scores in MDD patients. Increased cortical thickness at right orbital frontal responsible for decision making was correlated with severity of suicide. Further, increased functional activation at left auditory association cortex was a hallmark of hallucinations in MDD, which was directly associated with depression severity. Moreover, decreased spontaneous brain activity at right inferior frontal was also found, reflecting lower inhibition control in MDD patients. The abnormal structural and functional findings at fronto-cortical areas implied the dysfunctional cognitive control and emotion regulation in MDD. The alterations correlated with clinical scores might indicate the reliable neural markers for MDD.

Abstract Background The prognostic management of bladder cancer (BLCA) remains a great challenge for clinicians. Recently, bulk RNA-seq sequencing data have been used as a prognostic marker for many cancers but do not accurately detect core cellular and molecular functions in tumor cells. In the current study, bulk RNA-seq and single-cell RNA sequencing (scRNA-seq) data were combined to construct a prognostic model of BLCA. Methods BLCA scRNA-seq data were downloaded from Gene Expression Omnibus (GEO) database. Bulk RNA-seq data were obtained from the UCSC Xena. The R package "Seurat" was used for scRNA-seq data processing, and the uniform manifold approximation and projection (UMAP) were utilized for downscaling and cluster identification. The FindAllMarkers function was used to identify marker genes for each cluster. The limma package was used to obtain differentially expressed genes (DEGs) affecting overall survival (OS) in BLCA patients. Weighted gene correlation network analysis (WGCNA) was used to identify BLCA key modules. The intersection of marker genes of core cells and genes of BLCA key modules and DEGs was used to construct a prognostic model by univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Differences in clinicopathological characteristics, immune microenvironment, immune checkpoints, and chemotherapeutic drug sensitivity between the high and low-risk groups were also investigated. Results scRNA-seq data were analyzed to identify 19 cell subpopulations and 7 core cell types. The ssGSEA showed that all 7 core cell types were significantly downregulated in tumor samples of BLCA. We identified 474 marker genes from the scRNA-seq dataset, 1556 DEGs from the Bulk RNA-seq dataset, and 2334 genes associated with a key module identified by WGCNA. After performing intersection, univariate Cox, and LASSO analysis, we obtained a prognostic model based on the expression levels of 3 signature genes, namely MAP1B, PCOLCE2, and ELN. The feasibility of the model was validated by an internal training set and two external validation sets. Moreover, patients with high-risk scores are predisposed to experience poor OS, a larger prevalence of stage III-IV, a greater TMB, a higher infiltration of immune cells, and a lesser likelihood of responding favorably to immunotherapy. Conclusion By integrating scRNA-seq and bulk RNA-seq data, we constructed a novel prognostic model to predict the survival of BLCA patients. The risk score is a promising independent prognostic factor that is closely correlated with the immune microenvironment and clinicopathological characteristics.

Objective: Carotid artery computed tomography angiography (CTA) was used to analyze carotid atherosclerotic plaques and explore the correlation of plaque properties and other factors with the occurrence of acute ischemic stroke. The aim was to provide a basis for the prevention and treatment of acute ischemic stroke. Methods: Patients who underwent carotid artery CTA and magnetic resonance diffusion-weighted imaging (DWI) within 2 weeks before or after carotid artery CTA were analyzed retrospectively. Based on magnetic resonance DWI data, these patients were divided into the acute ischemic stroke group (n=95) and non-acute ischemic stroke group (n=102). The clinical data, laboratory data, and nature and surface morphology of the carotid plaques on CTA were compared between the two groups. Variables with P

Parkinson’s disease (PD) is a chronic neurodegenerative disease whose main pathological features are the degeneration of dopamine neurons and deposition of α-synuclein in neurons. At present, the most important treatment strategy for PD is drugs, and one of the most used drugs is levodopa. However, this therapy shows many problems, such as tolerance and long-term effects, so other treatment strategies need to be explored. As a traditional Chinese medicine treatment method with effective and few side effects, electroacupuncture is considered a non-drug therapy. It serves as a novel, promising therapeutic approach for the treatment of PD. In this review, the application and the effects of electroacupuncture on PD have been described. Besides, the underlying molecular mechanisms of electroacupuncture on PD that contribute to protecting dopaminergic neurons and reducing α-synuclein levels have been illustrated, including ① anti-oxidant stress response, ② anti-neuroinflammatory response, ③ up-regulation of neurotrophic factors and reduction of nerve cell apoptosis, ④ down-regulation of endoplasmic reticulum stress and improvement of mitochondrial function, ⑤ improvement of the function of the ubiquitin-proteasome system, ⑥ anti-excitatory toxicity response, ⑦ activation of autophagy, and ⑧ modulation of gut microbiota. Achieving a better understanding of the neuroprotective effects of electroacupuncture on PD will provide a theoretical basis and facilitate the application of electroacupuncture on PD.

Late spring cold is a disastrous weather condition that often affects early rice seedlings in southern China, limiting the promotion of direct seeding cultivation. However, there are few reports on the effect of these events and on the growth recovery mechanism of rice root systems after rice seedlings are exposed to this stress. This study selected the strong-growth-recovery variety B116 (R310/R974, F17) and the slow-recovery variety B811 (Zhonghui 286) for direct seeding cultivation and exposed them to low temperature and low-light stress to simulate a late spring cold event in an artificial climate chamber. The treatment consisted of 4 days of exposure to a day/night temperature of 14/10 °C and a light intensity of 266 µmol m−2s−1 while the control group was kept at a day/night temperature of 27/25 °C and light intensity of 533 µmol m−2s−1. The results showed that 6 days after stress, the total length, surface area, and volume of B116 roots increased by 335.5%, 290.1%, and 298.5%, respectively, while those of B811 increased by 228.8%, 262.0%, and 289.1%, respectively. In B116, the increase in root fresh weight was 223.1%, and that in B811 was 165.6%, demonstrating rapid root recovery after stress and significant differences among genotypes. The content of H2O2 and MDA in the B116 roots decreased faster than that in the B811 roots after normal light intensity and temperature conditions were restored, and the activity of ROS metabolism enzymes was stronger in B116 roots than in B811 roots. The correlation analysis between the transcriptome and metabolome showed that endogenous signal transduction and starch and sucrose metabolism were the main metabolic pathways affecting the rapid growth of rice seedling roots after exposure to combined stress from low temperature and low light intensities. The levels of auxin and sucrose in the roots of the strong-recovery variety B116 were higher, and this variety’s metabolism was downregulated significantly faster than that of B811. The auxin response factor and sucrose synthesis-related genes SPS1 and SUS4 were significantly upregulated. This study contributes to an understanding of the rapid growth recovery mechanism in rice after exposure to combined stress from low-temperature and low-light conditions.

To understand the association between cardiometabolic risk factor (CMRF) clustering and physical activity (PA) levels, we included 86520 Chinese adults aged 18–64 years having at least one CMRF (hypertension, diabetes, dyslipidemia, or obesity) from the China Chronic Disease and Nutrition Surveillance survey in 2015, a nationally and provincially representative investigation with a multistage clustering sampling design. Self-reported PA information was collected with the Global Physical Activity Questionnaire through face-to-face interviews. In view of the obesity epidemic in CMRF patients, PA energy expenditure (PAEE) per kilogram body weight was used, and was defined into four categories: (i) inactivity: 0 ​kJ/kg/day; (ii) low activity: 0–5 ​kJ/kg/day; (iii) moderate activity: 6–11 ​kJ/kg/day; and (iv) vigorous activity: ≥ 12 ​kJ/kg/day. The estimated weighted prevalence (95% confidence interval [CI]) of having 1, 2, 3, and 4 CMRFs was 60.57% (59.48%–61.67%), 28.10% (27.40%–28.79%), 9.82% (9.22%–15.42%) and 1.50% (1.37%–1.63%), respectively. The rate (95%CI) of inactivity, low activity, moderate activity, and vigorous activity was 34.52% (32.69%–36.35%), 22.22% (21.37%–23.37%), 15.98% (15.38%–16.58%) and 27.28% (26.02%–28.53%), respectively. For those having 2, 3 and 4 CMRFs (compared to those having 1 CMRF), the adjusted odds ratio (95%CI) for moderate activity and vigorous activity were 0.91 (0.85–0.98) and 0.92 (0.85–0.99), 0.87 (0.80–0.95) and 0.84 (0.77–0.92), and 0.77 (0.67–0.89) and 0.85 (0.72–1.00), respectively. In conclusion, CMRF clustering was a pandemic among Chinese adults in 2015 and was inversely associated with PA level. PAEE (in kJ/kg/day) may be introduced into PA management practice, especially for populations with high body weight.

Abstract Background To explore the optimal Mediterranean diet (MedDiet) adherence score threshold for the association between inflammatory markers and cognitive performance among older adults. Methods In this cross-sectional study, we selected data of the elderly (≥ 60 years old) from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 (n = 2830). Participants completed at least one cognitive measurement and two 24-h food recalls. By analyzing the relation between inflammatory markers and cognitive performance using the subdivided MedDiet adherence score, we got the optimal MedDiet adherence score threshold. Then the optimal threshold was used to divide participants into high and low MedDiet adherence groups and multivariate logistic regression models were developed to examine the association between inflammatory markers and cognitive performance in each group. Subgroup analysis was conducted based on gender, race, BMI, physical activity level, and chronic diseases. Results We chose 4 as the optimal MedDiet adherence score threshold and included these participants whose MedDiet adherence score was 4 or above into the high MedDiet adherence group, while the MedDiet adherence score of the low adherence group was less than 4. We found that the increased white blood cell (WBC) count (OR = 1.44, 95% CI: 1.09–1.90, P = 0.008), neutrophil count (OR = 1.30, 95% CI: 1.03–1.65, P = 0.023), and neutrophil-albumin ratio (NAR) (OR = 1.34, 95% CI: 1.06–1.70, P = 0.012) were all related to a higher risk of low cognitive performance in the low MedDiet adherence group. A higher PLR was linked to a reduced risk of low cognitive performance (OR = 0.86, 95% CI: 0.74–1.00, P = 0.036) in the high MedDiet adherence group. Significant differences were found in the associations of WBC count, neutrophil count and NAR with low cognitive performance between the low and high MedDiet adherence groups (all P

BackgroundMajor depressive disorder (MDD) is a disabling and severe psychiatric disorder with a high rate of prevalence, and adolescence is one of the most probable periods for the first onset. The neurobiological mechanism underlying the adolescent MDD remains unexplored.MethodsIn this study, we examined the cortical and subcortical alterations of neuroanatomical structures and spontaneous functional activation in 50 unmedicated adolescents with MDD vs. 39 healthy controls through the combined structural and resting-state functional magnetic resonance imaging.ResultsSignificantly altered regional gray matter volume was found at broader frontal-temporal-parietal and subcortical brain areas involved with various forms of information processing in adolescent MDD. Specifically, the increased GM volume at the left paracentral lobule and right supplementary motor cortex was significantly correlated with depression severity in adolescent MDD. Furthermore, lower cortical thickness at brain areas responsible for visual and auditory processing as well as motor movements was found in adolescent MDD. The lower cortical thickness at the superior premotor subdivision was positively correlated with the course of the disease. Moreover, higher spontaneous neuronal activity was found at the anterior cingulum and medial prefrontal cortex, and this hyperactivity was also negatively correlated with the course of the disease. It potentially reflected the rumination, impaired concentration, and physiological arousal in adolescent MDD.ConclusionThe abnormal structural and functional findings at cortico-subcortical areas implied the dysfunctional cognitive control and emotional regulations in adolescent depression. The findings might help elaborate the underlying neural mechanisms of MDD in adolescents.

Low temperature and overcast rain are harmful to directly seeding early rice, it can hinder rice growth and lower rice biomass during the seedling stage, which in turn lowers rice yield. Farmers usually use N to help rice recuperate after stress and minimize losses. However, the effect of N application on the growth recovery for rice seedlings after such low temperature stress and its associated physiological changes remain unclearly. Two temperature settings and four post-stress N application levels were used in a bucket experiment to compare B116 (strong growth recovery after stress) with B144 (weak growth recovery). The results showed that the stress (average daily temperature at 12°C for 4 days) inhibited the growth of rice seedlings. Compared to the zero N group, the N application group’s seedling height, fresh weight and dry weight significantly increased after 12 days. In particular, the increases in all three growth indicators were relatively higher than that of N application at normal temperature, indicating the importance of N application to rice seedlings after low temperature stress. The antioxidant enzyme activity of rice seedlings increased significantly after N application, which reduced the damaging effect of ROS (reactive oxygen species) to rice seedlings. At the same time, the soluble protein content of seedlings showed a slow decrease, while the H2O2 and MDA (malondialdehyde) content decreased significantly. Nitrogen could also promote nitrogen uptake and utilization by increasing the expression of genes related to NH4+ and NO3− uptake and transport, as well as improving the activity of NR (nitrate reductase) and GS (glutamine synthetase) in rice. N could affect GA3 (gibberellin A3) and ABA (abscisic acid) levels by regulating the anabolism of GA3 and ABA. The N application group maintained high ABA levels as well as low GA3 levels from day 0 to day 6, and high GA3 levels as well as low ABA levels from day 6 to day 12. The two rice varieties showed obvious characteristics of accelerated growth recovery and positive physiological changes by nitrogen application after stress, while B116 generally showed more obvious growth recovery and stronger growth-related physiological reaction than that of B144. The N application of 40 kg hm-2 was more conducive to the rapid recovery of rice growth after stress. The above results indicated that appropriate N application promoted rice seedling growth recovery after low temperature stress mainly by increasing the activities of antioxidant enzymes and nitrogen metabolizing enzymes as well as regulating the levels of GA3 and ABA. The results of this study will provide a reference for the regulation of N on the recovery of rice seedling growth after low temperature and weak light stress.

Introduction Neoadjuvant chemotherapy (NAC) has been demonstrated effective in several tumours, but its benefit has not yet been elucidated in colorectal cancer, especially locally advanced colorectal cancer (LACRC).Methods and analysis This is a single-arm, open-label, prospective phase II exploratory clinical trial. Patients with LACRC will receive four cycles of NAC with 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI), followed by operation and then adjuvant chemotherapy with capecitabine and oxaliplatin for two to five cycles or single-agent capecitabine for five cycles, or observation. The primary endpoint is the rate of tumour regression grade (TRG) 0–2 in the resected tumour tissue, which is evaluated by experienced pathologists according to the Ryan R TRG grading system. Secondary endpoints include objective response rate, pathologic complete response, microscopically complete resection rate, progression-free survival, distant metastasis-free survival, overall survival, toxicity and compliance to study treatment, molecular markers, quality of life to study treatment and the number of patients with 30-day postoperative mortality. The objective of this study is to analyse the efficacy and safety of FOLFOXIRI as the NAC regimen in patients with LACRC and to identify a promising treatment strategy in this setting.Ethics and dissemination Written informed consent will be required from and provided by all patients enrolled. The study protocol has been approved by the independent ethics committee of West China Hospital, Sichuan University (approval number: 2021403). This study will demonstrate the potential benefit of NAC with the FOLFOXIRI regimen. Results will be shared with policymakers and the academic community to promote the clinical management of colon cancer.Trial registration number NCT05018182.

BackgroundCognitive frailty is the coexistence of physical frailty and mild cognitive impairment. Research shows that cognitive frailty is related to an increased risk of hospitalization, mortality, disability, and dementia. Diabetes and hypertension are common risk factors for physical frailty and cognitive impairment. However, the factors influencing cognitive frailty in the elderly with hypertension and diabetes are still unclear. This study aimed to investigate the possible factors influencing cognitive frailty in the elderly with hypertension and diabetes.MethodsA cross-sectional study was conducted. We evaluated people over 60 years with hypertension and diabetes who underwent physical examination in Wuxi Xin'an Community Health Service Center. Frail scale, Montreal Cognitive Assessment-Basic and clinical dementia rating were used to assess cognitive frailty. We collected demographic characteristics, hypertension and diabetes-related laboratory indicators of the participants. We also used various scales to assess the overall health status of the elderly.ResultsApproximately 20.8% of the participants were determined to have cognitive frailty in elderly adults with hypertension and diabetes. These participants were older, had a lower monthly income, and included a higher proportion of peasants. They also had a higher level of depression (p = 0.037), higher risk of falls (p = 0.000), higher risk of malnutrition (p = 0.002), poorer ability to perform activities of daily living (ADL) (p = 0.000), and less social support (p = 0.030). Multivariate regression analysis was used to further assess the factors for cognitive frailty. After adjusting for possible confounders, age and ADL score emerged as risk factors, whereas high monthly income decreased the risk of cognitive frailty.ConclusionCognitive frailty is correlated with age, income, and ability to perform daily living activities in the elderly with diabetes and hypertension. Closer attention to the elderly who have low income and poor self-care ability may play an important role in the early prevention of cognitive frailty and even dementia.

The diameter at breast height (DBH) and location of trees are important factors when surveying forest resources and ecological functions. In this study, a device mainly comprising a self-made DBH-measuring instrument and positioning base station was used. The hardware consisted of two devices to simultaneously measure the DBH and location of trees within a sample plot. Specifically, DBH is acquired by processing angle data with an algorithm, and locations are obtained by a five-sided ranging and positioning algorithm based on the received signal strength indicator and ultra-wideband (UWB) sensor. Data uploading, storage and analysis are performed by an upper computer. The device was used for the actual measurement of eight 24 m × 24 m square plots. The measurements of this device are essentially consistent with those of the DBH tape and calliper, with biases of −0.03 cm and −0.29 cm, respectively. Compared with a compass for location measurement, the device had a mean range bias of 25.41 cm, overall bias along the X-axis of 2.40 cm and overall bias along the Y-axis of 1.99 cm. Therefore, the device is considered to be sufficiently portable and practical and can reduce the heavy workload for surveyors to meet the requirements of accurate and smart measurements in forest resource surveys.

Abstract Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase, which plays an essential role in both innate and adaptive immunity. However, the key molecular mechanisms that regulate SYK activity are poorly understood. Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation. We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK. This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors (CLRs), and also prevented the interaction with the phosphatase SHP-1. Therefore, deficiency of Trim31 in bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) dampened SYK-mediated signaling and inhibited the secretion of proinflammatory cytokines and chemokines against the fungal pathogen Candida albicans infection. Trim31 −/− mice were also more sensitive to C. albicans systemic infection than Trim31 +/+ mice and exhibited reduced Th1 and Th17 responses. Overall, our study uncovered the pivotal role of TRIM31-mediated K27-linked polyubiquitination on SYK activation and highlighted the significance of TRIM31 in anti-C. albicans immunity.

ObjectiveTo investigate the feasibility of 3D left ventricular global and regional strain by using one breath-hold (BH) compressed sensing cine (CSC) protocol and determine the agreement between CSC and conventional cine (CC) protocols.MethodsA total of 30 volunteers were enrolled in this study. Cardiovascular magnetic resonance (CMR) images were acquired using a 1.436 T magnetic resonance imaging (MRI) system. The CSC protocols included one BH CSC and the shortest BH CSC protocols with different parameters and were only performed in short-axis (SA) view following CC protocols. Left ventricular (LV) end-diastole volume (EDV), end-systole volume (ESV), stroke volume (SV), and ejection fraction (EF) global and regional strain were calculated by CC, one BH CSC, and shortest BH CSC protocols. The intraclass correlation coefficient (ICC) and coefficient of variance (CV) of these parameters were used to determine the agreement between different acquisitions.ResultsThe agreement of all volumetric variables and EF between the CC protocol and one BH CSC protocol was excellent (ICC > 0.9). EDV, ESV, and SV between CC and shortest BH CSC protocols also had a remarkable coherence (ICC > 0.9). The agreement of 3D LV global strain assessment between CC protocol and one BH CSC protocol was good (ICC > 0.8). Most CVs of variables were also good (CV < 15%). ICCs of all variables were lower than 0.8. CVs of all parameters were higher than 15% except global longitudinal strain (GLS) between CC and shortest BH CSC protocols. The agreement of regional strain between CC and BH CSC protocols was heterogeneous (-0.2 < ICC < 0.7). Many variables of CVs were poor.ConclusionNotably, one BH CSC protocol can be used for 3D global strain analysis, along with a good correlation with the CC protocol. The regional strain should continue to be computed by the CC protocol due to poor agreement and a remarkable variation between the protocols. The shortest BH CSC protocol was insufficient to replace the CC protocol for 3D global and regional strain.

The high-risk stroke populations are significantly associated with an increased risk of stroke or other vascular events. Although proven primary and secondary stroke prevention medications are available, persistent use is required to be effective. However, the persistence of drug therapy and its association with outcomes in the high-risk stroke population have received limited study in China. Hence, according to the China National Stroke Screening Survey (CNSSS) program in 2015, we performed this multicenter population-based cross-sectional survey and prospective cohort study in Sichuan of southwestern China. The residents aged ≥ 40 years volunteered to participate in a face-to-face survey in 8 communities. Subjects with at least three of eight stroke-related risk factors or a history of stroke were defined as high-risk stroke population. The interviewers recorded individuals' medications at a face-to-face survey, and all the high-risk stroke population was followed up for 4.7 years. The persistence of antihypertensives, hypoglycemics, lipid-lowering medications, and antithrombotics for stroke was evaluated. The primary outcome was new stroke. Secondary outcomes included new composite vascular events of stroke, myocardial infarction, and death during follow-up periods. Among 16,892 participants, 2,893 (17.1%) participants were high-risk stroke population and 2,698 (93.3%) participants completed to follow-up. The 4.7-year persistence of therapy rate of antihypertensives, hypoglycemics, lipid-lowering medications, and antithrombotics was 38.0%, 39.9%, 43.9%, and 59.8%, respectively. The total persistence of therapy rate for antihypertensives, hypoglycemics, lipid-lowering medications, and antithrombotics was 47.6% (136/286) in patients with hypertension, diabetes, dyslipidemia, and stroke at the same time. During the 4.7-year follow-up, there were 118 (4.4%) new ischemic stroke, 24 (0.9%) hemorrhagic stroke, 53 (2.0%) myocardial infarctions, and 33 (1.2%) deaths. After adjusting for the covariates, 4.7-year persistence of antihypertensives, hypoglycemics, lipid-lowering therapy, antithrombotics, and total persistence was independently associated with less new ischemic stroke and less new composite vascular events. Thus, more effective public education and efforts to understand and enhance the persistence of drug therapy are crucial to improve population health and decrease stroke and other vascular events for the high-risk stroke population.

Abstract Background Nitrogen application can effectively mitigate the damage to crop growth and yield caused by drought. However, the efficiency of heavy nitrogen application before drought (NBD) and heavy nitrogen application after drought (NAD) to regulate rice response to drought stress remains controversial. In this study, we profiled physiology, proteomics and metabolomics in rice variety Wufengyou 286 of two nitrogen management modes (NBD and NAD) to investigate their yield formation and the mechanism of nitrogen regulation for drought resistance. Results Results revealed that the yield of NBD and NAD decreased significantly when it was subjected to drought stress at the stage of young panicle differentiation, while the yield of NBD was 33.85 and 36.33% higher than that of NAD in 2017 and 2018, reaching significant levels. Under drought conditions, NBD increased chlorophyll content and net photosynthetic rate in leaves, significantly improved the activities of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase and catalase, and decreased malondialdehyde (MDA) content compared with NAD. NBD promoted nitrogen assimilation in leaves, which was characterized by increased activities of nitrate reductase (NR) and glutamine synthetase (GS). In addition, NBD significantly increased the contents of osmotic regulatory substances such as soluble sugar, soluble protein and free proline. Gene ontology and KEGG enrichment analysis of 234 differentially expressed proteins and 518 differential metabolites showed that different nitrogen management induced strong changes in photosynthesis pathway, energy metabolism pathway, nitrogen metabolism and oxidation-reduction pathways. Conclusion Different nitrogen management methods have significant differences in drought resistance of rice. These results suggest that heavy nitrogen application before drought may be an important pathway to improve the yield and stress resistance of rice, and provide a new ecological perspective on nitrogen regulation in rice.

BackgroundGallbladder squamous cell carcinoma (GSCC) is a rare carcinoma with limited evidence in literature, making it particularly difficult to study. Surveillance, Epidemiology, and End Results Database (SEER) were used to stress the clinicopathological features and outcomes associated with this tumor.MethodsSEER registries were used to identify GSCC and gallbladder adenocarcinoma (GAC) cases from 2004 to 2015. The Propensity matching (PSM) method was used for minimized potential difference between the two types and the utmost. Patients with GSCC versus GAC were compared using the clinicopathological features and outcomes.ResultsThere were 121 patients with GSCC and 6 580 patients had GAC. Compared with the GAC cohort, the GSCC cohort had a lower proportion of well-differentiated histology (3.3% vs. 12.1%, p < 0.001) and was diagnosed at a later T-stage (p < 0.001). Regarding treatment, patients treated with surgery, chemotherapy or radiation were associated with significantly better outcome than patients without undergoing these treatment modalities. In both univariate and multivariate analyses, GSCC histology was associated with worse prognosis than GAC histology.ConclusionsPatients with GSCC were associated with a worse outcome than the GAC cohort. The independent risk factors for patients with GSCC are surgery and chemotherapy.

With the aging of the population and the change of lifestyle in China, the prevalence and risk factors of the high-risk population for stroke may change. However, few studies performed community-based high-risk stroke population surveys in China. Hence, we performed this multicenter, cross-sectional, and community-based survey in Sichuan of southwestern China, according to the China National Stroke Screening Survey (CNSSS) program in 2015. The residents aged ≥ 40 years volunteered to participate in the face-to-face survey in 8 communities in Sichuan. The 8 communities were selected using the cluster randomization method. Subjects with at least three of the eight stroke-related risk factors were classified as a high-risk population for stroke. Otherwise were classified as a low-risk population for stroke. Furthermore, 1,011 individuals were randomly selected among the low-risk population for stroke as controls. Among 16,892 participants, 2,369 (14.0%) were high-risk population for stroke. After full adjustments, all eight risk factors for stroke were significantly associated with the high-risk population for stroke (P < 0.001). The largest contributor was hypertension [population-attributable risk (PAR) 28.4%], followed by physical inactivity (PAR 14.2%), dyslipidemia (PAR 11.2%), overweight/obesity (PAR 9.4%), diabetes (PAR 7.2%), family history (PAR 6.8%), smoking (PAR 5.9%), and atrial fibrillation (PAR 3.5%). Carotid atherosclerosis was more serious in the high-risk population for stroke than in controls (P < 0.05). The prevalence of the high-risk population for stroke was high in southwestern China. Hypertension, physical inactivity, and dyslipidemia were stronger contributors for the high-risk population for stroke. Individual-level and population-level interventions for these leading risk factors are very important for the primary prevention of stroke.

BackgroundPrevious preliminary studies have found that qigong exercises produced significant effects in healthy people and in various clinical populations. The purpose of this study was to systematically review the effects of qigong and tai chi exercise on individuals with drug addiction.MethodsA systematic search of seven English databases and three Chinese databases was conducted to identify randomized controlled trials (RCTs) and non-randomized comparative studies (NRS) assessing the effects of qigong and tai chi on drug addiction. Study quality was assessed using the Checklist for the Evaluation of Non-Pharmaceutical Trial Reports (CLEAR-NPT).ResultsTwo RCTs and nine NRS studies were included in this study, including a total of 1072 patients with drug addiction (age range, 27–43 years). The results showed that qigong and tai chi exercise had a significant overall effect on depression (SMD = −0.353, 95%CI [−0.548, −0.159]), anxiety (SMD = −0.541, 95%CI [−0.818, −0.264]), quality of life (SMD = 0.673, 95%CI [0.438, 0.907]), and sleep quality (SMD = −0.373, 95%CI [−0.631, −0.116]). The subgroup analysis found that qigong outperformed tai chi on the improving depression, anxiety, and sleep quality.ConclusionExisting studies suggest that qigong and tai chi are effective at improving depression, anxiety, and quality of life in drug users; however, the evidence from rigorous randomized controlled group trials is lacking.

Abstract Background Previous studies have acknowledged Tai Chi and Qigong exercise could be potential effective treatments for reducing depression and anxiety in both healthy and clinical populations. However, there is a scarcity of systematic reviews summarizing the clinical evidence conducted among individuals with substance use disorders. This study tries to fill up this gap. Methods A systematic search using Medline, EMbase, PsychINFO, Eric, SPORTDiscus, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese National Knowledge Infrastructure (CNKI), Wanfang, and the Chinese Scientific Journal (VIP) databases was initiated to identify randomized controlled trials (RCTs) and non-randomized comparison studies (NRS) assessing the effect of Tai Chi and Qigong versus various comparison groups on depression and anxiety related outcomes. Study quality was evaluated using a Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR-NPT) designed for nonpharmacological trial. Results One RCT and six NRS with a total of 772 participants were identified. Some of them were meta-analyzed to examine the pooled effects based on different types of intervention and controls. The results of meta-analyses suggested the effect of Tai Chi was comparable to treatment as usual (TAU) on depression (standardized mean difference (SMD) = − 0.17[− 0.52, 0.17]). Qigong exercise appears to result in improvement on anxiety compared to that of medication (SMD = -1.12[− 1.47, − 0.78]), and no treatment control (SMD = -0.52[− 0.77, − 0.27]). Conclusion The findings suggest potentially beneficial effect of Qigong exercise on symptoms of anxiety among individuals with drug abuse. Considering the small number and overall methodological weakness of included studies and lack of RCTs, results should be interpreted with caution and future rigorously designed RCTs are warranted to provide more reliable evidence.

Abstract Ramie (Boehmeria nivea L. Gaud) suffers from long-term continuous cropping. Here, using Illumina high-throughput sequencing technology, we aimed to identify bacteria and fungi associated with continuous cropping in ramie fields in Yuanjiang, Xianning, Sichuan, and Jiangxi. The rarefaction results showed that Jiangxi had significantly lower bacterial α-diversity than that of the other areas. Firmicutes, Proteobacteria, and Acidobacteria were the dominant bacterial phyla, and Ascomycota, Basidiomycota, and Zygomycota were the dominant fungal phyla. In Jiangxi, Firmicutes accounted for 79.03% of all valid reads, which could have significant decreased microbial diversity and negative effects of continuous ramie cropping. We used traditional methods to examine soil nutrients. Sichuan had a relatively high pH and available P and K, but low total N; opposite findings were recorded in Jiangxi. The redundancy analysis revealed that the urease activity, PH, available K, and total N significantly correlated with bacterial community abundance, whereas only total N significantly correlated with fungal community abundance (P

Abstract Background Stroke and its risk factors epidemiological survey can help identify individuals at higher risk and therefore promote stroke prevention strategies. The aim of this study was to estimate the current prevalence of stroke and high risk stroke population, and evaluate stroke associated risk factors in southwestern China. Methods This was a multi-center, cross sectional survey in southwestern China from May 2015 to September 2015. The eight communities were selected at random, and 17,413 residents aged ≥40 years volunteered to participate in this survey. Data were collected through face-to-face survey using a structured questionnaire. Five hundred twenty-one participants with incomplete questionnaires on stroke history or risk factors records were excluded. Results A total of 16,892 people included in analysis. The overall prevalence of stroke was 3.1% (95% CI 2.6–3.9%), 17.1% of participants were the high risk stroke population. After full adjustments, hypertension, diabetes, dyslipidemia, overweight, lack of exercise and family history of stroke were significantly associated with overall stroke and ischemic stroke. The largest contributor was hypertension (population-attributable risk 23.6%), followed by dyslipidemia, physical inactivity, family history of stroke, diabetes, and overweight. However, only hypertension (OR = 3.66, 95% CI 1.82–8.23) was significantly associated with hemorrhagic stroke. Conclusions The prevalence of stroke and high risk stroke population was high among adults aged ≥40 years in southwestern China. Hypertension, dyslipidemia and lack of exercise were stronger contributors for stroke, these findings suggest that individual-level and population-level interventions for these leading risk factors are necessary to prevent stroke.

Abies beshanzuensis, an extremely rare and critically endangered plant with only three wild adult trees globally, is strongly mycorrhizal-dependent, leading to difficulties in protection and artificial breeding without symbiosis. Root hair morphogenesis plays an important role in the survival of mycorrhizal symbionts. Due to the lack of an effective genome and transcriptome of A. beshanzuensis, the molecular signals involved in the root hair development remain unknown, which hinders its endangered mechanism analysis and protection. Herein, transcriptomes of radicles with root hair (RH1) and without root hair (RH0) from A. beshanzuensis in vitro plantlets were primarily established. Functional annotation and differentially expressed gene (DEG) analysis showed that the two phenotypes have highly differentially expressed gene clusters. Transcriptome divergence identified hormone and sugar signaling primarily involved in root hair morphogenesis of A. beshanzuensis. Weighted correlation network analysis (WGCNA) coupled with quantitative real-time PCR (qRT-PCR) found that two hormone–sucrose–root hair modules were linked by IAA17, and SUS was positioned in the center of the regulation network, co-expressed with SRK2E in hormone transduction and key genes related to root hair morphogenesis. Our results contribute to better understanding of the molecular mechanisms of root hair development and offer new insights into deciphering the survival mechanism of A. beshanzuensis and other endangered species, utilizing root hair as a compensatory strategy instead of poor mycorrhizal growth.

Cervical carcinosarcoma (CCS) is a rare aggressive tumor which was referred to as a sarcoma initially with its morbidity less than 1% of all cervical cancers. Four theories have been proposed for the pathogenesis of CCS. The “metaplastic theory,” also called “monoclonal theory,” has been widely accepted so far. The most common clinical symptom of CCS is abnormal vaginal bleeding. CCS is much less common than the counterparts in uterine corpus and usually confused with uterine carcinosarcoma (UCS) or common cervical cancer. The management for CCS has been mainly extrapolated from studies of UCS or cervical cancers. However, CCS has its special anatomical position and biological behaviors and is usually diagnosed at an early stage than UCS. Currently, there is no consensus on the survival, management and prognosis factors of CCS. We reviewed and summarized the literatures regarding to the epidemiology, clinical presentations, pathogenesis, diagnosis and treatment of CCS for providing clinicians with comprehensive information to diagnose and treat this malignancy.

Chinese yam, with its rich taste and high nutritive value, has remained an essential part of Chinese cuisine. As China is rich in yam germplasm resources, understanding the genetic diversity of local varieties, which is important for the proper management, conservation, variety improvement, and sustainable utilization of yam germplasms, is crucial. In this study, an Illumina Hi-seq 2500 sequencing (Illumina, San Diego, CA, USA) system was used to sequence cDNA libraries of root, stem, and leaf tissues of Chinese yam; 14,450 unigenes containing SSR sites were identified from the transcriptome dataset. About half of the SSRs were mononucleotides and approximately 23% were dinucleotides and trinucleotides. In addition, 100 SSR primers were randomly designed for PCR and polymorphism verification. A total of 32 yam materials used in the study were identified by 24 primer pairs. Based on the Qinling-Huaihe River line, the northern and southern germplasms were divided into different taxa, but no clear geographical pattern was observed in the southern germplasms. The 32 germplasms were also divided into three categories using a clustering analysis, with samples in the same group possessing similar morphological characters. These 24 newly identified SSR markers can provide the basis for the genetic identification, diversity analysis, and marker-assisted selection breeding of Dioscoreaceae.

Self-resistance determinants are essential for the biosynthesis of bioactive natural products and are closely related to drug resistance in clinical settings. The study of self-resistance mechanisms has long moved forward on the discovery of new resistance genes and the characterization of enzymatic reactions catalyzed by these proteins. However, as more examples of self-resistance have been reported, it has been revealed that the enzymatic reactions contribute to self-protection are not confined to the cellular location where the final toxic compounds are present. In this review, we summarize representative examples of self-resistance mechanisms for bioactive natural products functional at different cell locations to explore the models of resistance strategies involved. Moreover, we also highlight those resistance determinants that are widespread in nature and describe the applications of self-resistance genes in natural product mining to interrogate the landscape of self-resistance genes in drug resistance-related new drug discovery.

Background: The purpose of this study was to systematically review the effectiveness of Tai Chi and Qigong exercise on adolescents' symptoms of depression and anxiety, and psychological status based on clinical evidences, and to calculate the pooled results using meta-analysis.Methods: A systematic search using seven English and three Chinese databases was initiated to identify randomized controlled trials (RCT) and non-randomized comparison studies (NRS) assessing the effect of Tai Chi and Qigong exercise on psychological status among adolescents. Standardized mean differences (SMD) and their 95% confidence intervals (CI) were used to determine the pooled effect of the intervention. Study quality was evaluated using a Checklist to Evaluate a Report of a Non-pharmacological Trial (CLEAR-NPT) designed for non-pharmacological trials.Results: Four RCTs and six NRS were identified, including 1,244 adolescents. The results suggested a potential beneficial effect of Tai chi and Qigong exercise on reducing anxiety (SMD = 0.386, 95 CI% [0.233, 0.538]) and depression (SMD = 1.937 [95 CI%, 1.392–2.546]) symptoms, and reducing cortisol level (SMD = 0.621 [95 CI%, 0.18–1.062]) in adolescents. Conversely, non-significant effects were found for stress, mood, and self-esteem.Conclusions: The findings of this review suggest Qigong appears to be an effective therapeutic modality to improve psychological well-being in adolescents. Hope future studies will have rigorously designed, well-controlled randomized trials with large sample sizes in order to confirm these findings.

Intra-abdominal desmoplastic small round cell tumor (IDSRCT) is a rare and highly malignant soft tissue neoplasm, which is characterized by rapid progression and poor prognosis. The mechanism underlying the development of this neoplasm remains elusive, but all cases are characterized by the chromosomal translocation t (11;22) (p13; q12), which results in a formation of EWSR1-WT1 gene fusion. The diagnosis of IDSRCT is often made with core-needle tissue biopsy specimens or laparoscopy or laparotomy. Immunohistochemical analyses have shown the co-expression of epithelial, neuronal, myogenic, and mesenchymal differentiation markers. FISH or reverse transcription polymerase chain reaction detecting EWS-WT1 fusion can be performed to assist in molecular confirmation. There is no standard of care for patients with IDSRCT currently, and majority of newly diagnosed patients received the aggressive therapy, which includes >90% resection of surgical debulking, high-dose alkylator-based chemotherapy, and radiotherapy. More recently, targeted therapy has been increasingly administered to recurrent IDSRCT patients and has been associated with improved survival in clinical conditions. Immunotherapy as a possible therapeutic strategy is being explored in patients with IDSRCT. In this review, we summarize currently available knowledge regarding the epidemiology, potential mechanisms, clinical manifestations, diagnosis, treatment, and prognosis of IDSRCT to assist oncologists in comprehensively recognizing and accurately treating this malignancy.

Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status of tumors is a distinct predictive biomarker of immune checkpoint inhibitors (ICIs) for colorectal and non-colorectal cancer populations. The overall response rate (ORR) varies from approximately 40% to 60%, indicating that nearly half of MSI-H tumors do not respond to ICIs. The mechanism of response heterogeneity in MSI-H/dMMR cancers is unclear. Some patients who have been treated with ICIs have developed a novel pattern of progression called hyperprogression, which is defined as unexpected accelerated tumor growth. No case of MSI-H/dMMR immunotherapy-associated hyperprogression has been reported in the literature. Here, we present the case of a patient with dMMR gastrointestinal cancer who suffered hyperprogressive disease (HPD) after treatment with nivolumab. We explored the potential mechanisms of HPD by clinical, immune, and genomic characteristics. Extremely high levels of serum LDH, low TMB and TILs, and the disruption of TGFβ signaling, may be related to hyperprogression.

“Late spring coldness” (T) is a frequent meteorological disaster in the spring in southern China, often causing severe yield losses of direct-seeded early rice. In this study, we investigated the mechanisms underlying the differences in the compensatory growth ability of different rice genotypes by focusing on agronomic traits, physiological indicators, and transcriptome. The results showed that there were significant differences in the compensatory growth recovery ability of different genotypes after a combination of four days of low temperature and weak light stress. Only the strong compensatory growth genotype B116 was able to grow rapidly and reduce soluble protein and H2O2 concentrations rapidly after stress. By analyzing enzyme activity as well as endogenous hormone concentration, we found that the high superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities and high levels of abscisic acid (ABA) could reduce the damage of B116 during stress. Meanwhile, higher glutamine synthetase (GS) and nitrate reductase (NR) activity and higher levels of gibberellin A3(GA3), indoleacetic acid (IAA), and zeatin nucleoside (ZR) could enable B116 to grow rapidly after stress. The identified differentially expressed genes (DEGs) indicated that there were large differences in POD-related genes and gibberellin metabolism between B116 and B144 after stress; RT-PCR quantification also showed a trend consistent with RNA-seq, which may be an important reason for the differences in compensatory growth ability.

The panicle apical abortion (PAA) causes severe yield losses in rice production, but details about its development and molecular basis remain elusive. Here, we detected PAA quantitative trait loci (QTLs) in three environments using a set of chromosome segment substitution lines (CSSLs) that was constructed with indica Changhui121 as the recurrent parent and japonica Koshihikari as the donor parent. First, we identified a novel major effector quantitative trait locus, qPAA7, and selected a severe PAA line, CSSL176, which had the highest PAA rate among CSSLs having Koshihikari segments at this locus. Next, an F2 population was constructed from a cross between CSS176 and CH121. Using F2 to make recombinantion analysis, qPAA7 was mapped to an 73.8-kb interval in chromosome 7. Among nine candidate genes within this interval, there isn’t any known genes affecting PAA. According to the gene annotation, gene expression profile and alignment of genomic DNA, LOC_Os07g41220 and LOC_Os07g41280 were predicted as putative candidate genes of qPAA7. Our study provides a foundation for cloning and functional characterization of the target gene from this locus.

Suicide is a leading cause of death among youth and is strongly associated with major depressive disorder (MDD). However, the neurobiological underpinnings of suicidal behaviour and the identification of risk for suicide in young depressed patients are not yet well-understood. In this study, we used a seed-based correlation analysis to investigate the differences in resting-state functional connectivity (RSFC) in depressed youth with or without a history of suicide attempts and healthy controls (HCs). Suicidal attempters (ATT group, n = 35), non-suicide attempters (NAT group, n = 18), and HCs exhibited significantly different RSFC patterns with the left superior prefrontal gyrus (L-SFG) and left middle prefrontal gyrus (L-MFG) serving as the regions of interest (ROIs). The ATT group showed decreased RSFC of the left middle frontal gyrus with the left superior parietal gyrus compared to the NAT and HC groups. Decreased RSFC between the left superior frontal gyrus and the right anterior cingulate cortex (rACC) was found in the ATT group compared to the NAT and HC groups. Furthermore, the left prefrontal-parietal connectivity was associated with suicidal ideation and levels of impulsivity, but RSFC of the left prefrontal cortex with the rACC was correlated exclusively with impulsivity levels and was not related to suicidal ideation in the ATT group. Our results demonstrated that altered RSFC of the prefrontal-parietal and prefrontal-rACC regions was associated with suicide attempts in depressed youth, and state-related deficits in their interconnectivity may contribute to traits, such as cognitive impairments and impulsivity to facilitate suicidal acts. Our findings suggest that the neural correlates of suicidal behaviours might be dissociable from those related to the severity of current suicidal ideation. Neural circuits underlying suicide attempts differ from those that underlie suicidal ideation.

Abstract Background Community health services have played an important role in the prevention and control of diabetes in China. The aims of this study were to examine the frequency of visits to community clinics for diabetic care services, to assess factors correlated with infrequent primary care visits and to identify barriers to regular follow-up visits for urban and rural patients. Methods Between October 2014 and November 2014, data were collected from 17 communities in two cities and four townships located in Shandong and Jiangsu Provinces in China. A total of 1598 diabetic patients aged 18 years or older who were registered with a primary health station in local communities were selected by simple random sampling. Each participant was required to complete an interviewer-led questionnaire. Univariate and multivariate analyses were used to identify significant factors for infrequent visitor status using multivariable logistic regression analysis. Results After being clearly informed of the study protocol, 1508/1598 (94.4%) patients agreed to participate in this survey. Among the 1508 subjects (mean age 64.4 ± 10.6), 683 (45.3%) were classified as infrequent visitors. The following were significant factors determining infrequent visitor status: urban residence, lack of health insurance, per-capita household income

Abstract Background The crop growth compensation effect is a naturally biological phenomenon, and nitrogen (N) is essential for crop growth and development, especially for yield formation. Little is known about the molecular mechanism of N deficiency and N compensation in rice. Thus, the N-sensitive stage of rice was selected to study N deficiency at the tillering stage and N compensation at the young panicle differentiation stage. In this study, a proteome analysis was performed to analyze leaf differentially expressed proteins (DEPs), and to investigate the leaf physiological characteristics and yield under N deficiency and after N compensation. Results The yield per plant presented an equivalent compensatory effect. The net photosynthetic rate, optimal/maximal quantum yield of photosystem II (Fv/Fm), soil and plant analyzer development (SPAD) value, and glutamic pyruvic transaminase (GPT) activity of T1 (N deficiency at the tillering stage, and N compensation at the young panicle differentiation stage) were lower than those of CK (N at different stages of growth by constant distribution) under N deficiency. However, after N compensation, the net photosynthetic rate, Fv/Fm, SPAD value and GPT activity were increased. Using an iTRAQ-based quantitative approach, a total of 1665 credible proteins were identified in the three 4-plex iTRAQ experiments. Bioinformatics analysis indicated that DEPs were enriched in photosynthesis, photosynthesis-antenna proteins, carbon metabolism and carbon fixation in the photosynthetic organism pathways. Moreover, the photosynthesis-responsive proteins of chlorophyll a-b binding protein, ribulose bisphosphate carboxylase small chain and phosphoglycerate kinase were significantly downregulated under N deficiency. After N compensation, chlorophyll a-b binding protein, NADH dehydrogenase subunit 5, NADH dehydrogenase subunit 7, and peroxidase proteins were significantly upregulated in rice leaves. Conclusion Through physiological and quantitative proteomic analysis, we concluded that a variety of metabolic pathway changes was induced by N deficiency and N compensation. GO and KEGG enrichment analysis revealed that DEPs were significantly associated with photosynthesis pathway-, energy metabolism pathway- and stress resistance-related proteins. The DEPs play an important role in the regulation of N deficiency and the compensation effect in rice.

Background: Exercise therapy was suggested as an appealing treatment option for Adolescent Idiopathic Scoliosis (AIS) patients with less side effects, lower economic costs, and more psychological benefits. Nevertheless, no unanimous findings about the efficacy of exercise therapy have been obtained from previous systematic reviews and/or meta-analyses. Objective: To provide an overview of previous systematic reviews and/or meta-analyses on the effectiveness of exercise therapy on AIS treatment. Methods: Systematic searches in Medline, Eric, CINAHL, Embase, SPORTDiscus, PsycINFO, and the Cochrane Library for systematic reviews and/or meta-analyses of randomized controlled trials (RCTs), non-randomized comparison studies (NRS) or observational studies using exercise as an intervention, and with outcome measures including Cobb angle, angle of trunk rotation (ATR), and quality of life. The methodological quality of the review articles was evaluated by A Measurement Tool to Assess Systematic Reviews (AMSTAR) checklist. Results: Ten systematic reviews and meta-analyses were included. The quality of most of the review articles is moderate with a mean score of 6/11 on the AMSTAR scale. Overall, there is increasing evidence showing the efficacy of exercise therapy on reducing the Cobb angle and angle of trunk rotation, and improving perceived quality of life. Conclusion: Exercise therapy was found to have potential benefits to treat physiological and psychological aspects of AIS patients. However, the findings were not conclusive given that some reviews relied on data from the trials with potential risk of bias and significant heterogeneity. More high-quality research is still needed to verify these findings.

Hexagonal boron nitride nanosheets (h-BNNs) show great potential in the field of tribology due to their typical two-dimensional layered structure and are essential for replacing conventional sulfur/phosphate-containing additives. However, the large particle size and poor dispersion of h-BNs seriously restrict their green lubrication application. In this paper, MnO2@h-BNNs nanocomposites were successfully prepared by ultrasonically exfoliating a hydrothermal method. The tribological properties of MnO2@h-BNNs nanocomposites as lubricant additives in poly-alpha-olefin oil (PAO) were investigated. The results show the oil dispersed with 0.25 wt% MnO2@h-BNNs had the best friction reduction and antiwear effect with 42% and 11.2% reduction, respectively, compared with the plain oil. Through further wear surface analyzing, we verified the antiwear mechanism of additives in filling the micropits and grooves on the wear surface and forming a friction protection film including Fe2O3, MnO2, and BN on the wear surface, avoiding direct contact between the friction subsets. This can provide ideas for other lubricating oil additives.

Abstract Background Long non-coding RNAs (lncRNAs) have been found to play a vital role in several gene regulatory networks involved in the various biological processes in plants related to stress response. However, systematic analyses of lncRNAs expressed in rice Cadmium (Cd) stress are seldom studied. Thus, we presented the characterization and expression of lncRNAs in rice root development at an early stage in response to Cd stress. Results The lncRNA deep sequencing revealed differentially expressed lncRNAs among Cd stress and normal condition. In the Cd stress group, 69 lncRNAs were up-regulated and 75 lncRNAs were down-regulated. Furthermore, 386 matched lncRNA-mRNA pairs were detected for 120 differentially expressed lncRNAs and 362 differentially expressed genes in cis, and target gene-related pathway analyses exhibited significant variations in cysteine and methionine metabolism pathway-related genes. For the genes in trans, overall, 28,276 interaction relationships for 144 lncRNAs and differentially expressed protein-coding genes were detected. The pathway analyses found that secondary metabolites, such as phenylpropanoids and phenylalanine, and photosynthesis pathway-related genes were significantly altered by Cd stress. All of these results indicate that lncRNAs may regulate genes of cysteine-rich peptide metabolism in cis, as well as secondary metabolites and photosynthesis in trans, to activate various physiological and biochemical reactions to respond to excessive Cd. Conclusion The present study could provide a valuable resource for lncRNA studies in response to Cd treatment in rice. It also expands our knowledge about lncRNA biological function and contributes to the annotation of the rice genome.