Metabolic Syndrome Is Associated With an Increased Risk of Rheumatoid Arthritis: A Prospective Cohort Study Including 369,065 Participants.

OBJECTIVE: To explore the associations between metabolic syndrome (MetS) and its individual components and the risk of rheumatoid arthritis (RA). METHODS: A total of 369,065 individuals were included in the present study based on the UK Biobank. Multivariable Cox proportional hazards regression models were applied to estimate the associations between MetS and its individual components and the risk of RA. Mediation analysis was performed to further assess the potential mediating role of C-reactive protein (CRP) in the relationship between MetS and RA. RESULTS: During a median follow-up period of 12.04 years, a total of 4901 incident RA cases were documented. MetS (hazard ratio [HR] 1.22, 95% CI 1.14-1.30) and 4 of its 5 components (elevated waist circumference [WC; HR 1.21, 95% CI 1.12-1.32], elevated triglyceride [TG] level [HR 1.12, 95% CI 1.05-1.19], reduced high-density lipoprotein cholesterol [HDL-C] level [HR 1.31, 95% CI 1.23-1.39], and hyperglycemia [HR 1.15, 95% CI 1.05-1.25]) were associated with an increased risk of RA. In addition, the risk of RA increased as the number of diagnosed MetS components increased, with the highest risk in participants with all 5 components. Mediation analysis showed that CRP might mediate the association between MetS and RA, accounting for 9.27% of the total effect. CONCLUSION: These findings indicated positive associations between MetS and 4 of its components (WC, TG, HDL-C, and hyperglycemia) and the risk of RA, highlighting the importance of MetS management in the prevention of RA.

Auricular Vagal Nerve Stimulation Inhibited Central Nerve Growth Factor/Tropomyosin Receptor Kinase A/Phospholipase C-Gamma Signaling Pathway in Functional Dyspepsia Model Rats With Gastric Hypersensitivity.

OBJECTIVE: Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation (AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating the activity of the vagus nerve. However, the potential molecular mechanism is still unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity. MATERIALS AND METHODS: We established the FD model rats with gastric hypersensitivity by means of colon administration of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally), and K252a + AVNS were performed on eight-week-old model rats for five consecutive days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by the measurement of abdominal withdrawal reflex response to gastric distention. NGF in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid 1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase chain reaction, Western blot, and immunofluorescence tests. RESULTS: It was found that a high level of NGF in gastric fundus and an upregulation of the NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile, both AVNS treatment and the administration of K252a not only decreased NGF messenger ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the molecular expressions of the signal pathway than did the K252a treatment. CONCLUSION: AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS in ameliorating visceral hypersensitivity in FD model rats.

Exogenous Substances Used to Relieve Plants from Drought Stress and Their Associated Underlying Mechanisms.

Drought stress (DS) is one of the abiotic stresses that plants encounter commonly in nature, which affects their life, reduces agricultural output, and prevents crops from growing in certain areas. To enhance plant tolerance against DS, abundant exogenous substances (ESs) have been attempted and proven to be effective in helping plants relieve DS. Understanding the effect of each ES on alleviation of plant DS and mechanisms involved in the DS relieving process has become a research focus and hotspot that has drawn much attention in the field of botany, agronomy, and ecology. With an extensive and comprehensive review and summary of hundred publications, this paper groups various ESs based on their individual effects on alleviating plant/crop DS with details of the underlying mechanisms involved in the DS-relieving process of: (1) synthesizing more osmotic adjustment substances; (2) improving antioxidant pathways; (3) promoting photosynthesis; (4) improving plant nutritional status; and (5) regulating phytohormones. Moreover, a detailed discussion and perspective are given in terms of how to meet the challenges imposed by erratic and severe droughts in the agrosystem through using promising and effective ESs in the right way and at the right time.

Multi-Omics Analysis of Gut Microbiota and Host Transcriptomics Reveal Dysregulated Immune Response and Metabolism in Young Adults with Irritable Bowel Syndrome.

The integrated dysbiosis of gut microbiota and altered host transcriptomics in irritable bowel syndrome (IBS) is yet to be known. This study investigated the associations among gut microbiota and host transcriptomics in young adults with IBS. Stool and peripheral blood samples from 20 IBS subjects and 21 healthy controls (HCs) collected at the baseline visit of an RCT were sequenced to depict the gut microbiota and transcriptomic profiles, respectively. The diversities, composition, and predicted metabolic pathways of gut microbiota significantly differed between IBS subjects and HCs. Nine genera were significantly abundant in IBS stool samples, including Akkermansia, Blautia, Coprococcus, Granulicatella, Holdemania, Oribacterium, Oscillospira, Parabacteroides, and Sutterella. There were 2264 DEGs found between IBS subjects and HCs; 768 were upregulated, and 1496 were downregulated in IBS participants compared with HCs. The enriched gene ontology included the immune system process and immune response. The pathway of antigen processing and presentation (hsa04612) in gut microbiota was also significantly different in the RNA-seq data. Akkermansia, Blautia, Holdemania, and Sutterella were significantly correlated with ANXA2P2 (upregulated, positive correlations), PCSK1N (downregulated, negative correlations), and GLTPD2 (downregulated, negative correlations). This study identified the dysregulated immune response and metabolism in IBS participants revealed by the altered gut microbiota and transcriptomic profiles.

COVID-19 mRNA vaccine, but not a viral vector-based vaccine, promotes neutralizing anti-type I interferon autoantibody production in a small group of healthy individuals.

Coronavirus disease 2019 (COVID-19) vaccines are highly effective but also induce adverse events, in particular, autoimmunity. Findings from several studies revealed that patients with life-threatening SARS-CoV-2 infection had increased, pre-existing, neutralizing antibodies against type I interferons (IFNs). However, whether COVID-19 vaccination induces the anti-type I IFN antibody remains unclear. In the current study, we evaluated plasma levels of 103 autoantibodies against various human self-antigens and 16 antibodies against viral antigens in healthy individuals pre- and post-COVID-19 vaccination. Twelve participants received a COVID-19 mRNA vaccine (Pfizer-BioNTech or Moderna), and 8 participants received a viral vector-based vaccine (Janssen). All participants produced increased antibody levels against SARS-CoV-2 antigens following vaccination. Among the 103 autoantibodies, only plasma levels of IgG autoantibodies against type I IFNs increased in participants who received a mRNA vaccine (3/12), but not in those who received the viral vector-based vaccine (0/8) at postvaccination compared to pre-vaccination. Among the three individuals showing increased anti-IFN IgG following vaccination, both plasma samples and plasma-purified total IgGs showed a dose-dependent binding ability to IFN-α; two of the three showed neutralizing activity to IFN-α-2a-induced phosphorated STAT1 responses in human peripheral blood mononuclear cells postvaccination compared to baseline in vitro. Among the 103 autoantibodies tested, the COVID-19 mRNA vaccine, but not the viral vector-based vaccine, specifically induced neutralizing anti-type I IFN autoantibodies in a small group of healthy individuals (~10%). Findings from this study imply that COVID-19 mRNA vaccines may suppress IFN-mediated innate immunity and impair immune defense through induced autoimmunity in some healthy individuals, who may need to switch to another type of COVID-19 vaccine (e.g., a viral vector-based vaccine).

COVID-19 is associated with bystander polyclonal autoreactive B cell activation as reflected by a broad autoantibody production, but none is linked to disease severity.

Coronavirus disease 2019 (COVID-19) is associated with autoimmune features and autoantibody production in a small subset of the population. Pre-existing neutralizing antitype I interferons (IFNs) autoantibodies are related to the severity of COVID-19. Plasma levels of IgG and IgM against 12 viral antigens and 103 self-antigens were evaluated using an antibody protein array in patients with severe/critical or mild/moderate COVID-19 disease and uninfected controls. Patients exhibited increased IgGs against Severe acute respiratory syndrome coronavirus-2 proteins compared to controls, but no difference was observed in the two patient groups. 78% autoreactive IgGs and 93% autoreactive IgMs were increased in patients versus controls. There was no difference in the plasma levels of anti-type I IFN autoantibodies or neutralizing anti-type I IFN activity of plasma samples from the two patient groups. Increased anti-type I IFN IgGs were correlated with higher lymphocyte accounts, suggesting a role of nonpathogenic autoantibodies. Notably, among the 115 antibodies tested, only plasma levels of IgGs against human coronavirus (HCOV)-229E and HCOV-NL63 spike proteins were associated with mild disease outcome. COVID-19 was associated with a bystander polyclonal autoreactive B cell activation, but none of the autoantibody levels were linked to disease severity. Long-term humoral immunity against HCOV-22E and HCOV-NL63 spike protein was associated with mild disease outcome. Understanding the mechanism of life-threatening COVID-19 is critical to reducing mortality and morbidity.

Effects of biochar addition on aeolian soil microbial community assembly and structure.

The effects of biochar on soil improvement have been widely confirmed, but its influence on soil microorganisms is still unclear. Elucidating the complex relationship and the community assembly processes of microorganisms under biochar addition is important to understand the ecological effects of this substance. We performed a one-time addition of biochar on aeolian soils and planted maize (Zea mays L.) continuously for 7 years. Afterwards, soil samples were collected, and the 16S/ITS rRNA gene sequencing technology was used to study changes in microbial community structure, network characteristics, and community assembly processes in the aeolian soils. We found that biochar addition significantly increased the maize yield and changed the soil microbial community composition (ß-diversity), but had no significant effect on the microbial α-diversity. The addition of 31.5-126.0 Mg ha-1 of biochar led to a reduction of the rhizosphere bacterial network's edge number, average degree, and robustness, but had no significant effect on the fungal network properties. The bacterial community was controlled by deterministic processes, while fungi were mainly controlled by stochastic processes. The addition of 126.0 Mg ha-1 of biochar led to a transformation of the bacterial community's assembly processes from deterministic to stochastic. These results indicate that the stability of the rhizosphere bacterial community's complex network in aeolian soils diminishes under biochar addition, together changed the bacterial community's assembly processes. Fungi can instead effectively resist the environmental changes brought by biochar addition, and their network remains unchanged. These findings help clarify the effect of biochar addition on microbial interaction and assembly processes in aeolian soils characteristic of arid regions. KEY POINTS: • Biochar addition led to changes in the microbial community composition • Biochar addition reduced the network's stability of rhizosphere bacteria • Biochar addition changed the processes of the bacterial community assembly.

Serum metabolomics probes the molecular mechanism of action of acupuncture on metabolic pathways related to glucose metabolism in patients with polycystic ovary syndrome-related obesity.

Polycystic ovary syndrome (PCOS) is a common endocrine syndrome, and obesity is the most common clinical manifestation. Acupuncture is effective in treating PCOS, but the differences in the biological mechanisms of acupuncture therapy and Western medicine treatment have not been determined. Thus, the purpose of this study was to find glucose metabolism-related pathways in acupuncture treatment and differentiate them from Western medical treatment. Sixty patients with PCOS-related obesity were randomly distributed into three groups: patients receiving (1) acupuncture treatment alone, (2) conventional Western medicine treatment, and (3) acupuncture combined with Western medicine treatment. A targeted metabolomics approach was used to identify small molecules and metabolites related to glucose metabolism in the serum of each group, and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze different metabolic fractions. The results showed acupuncture treatment modulates the activity of citric and succinic acids in the tricarboxylic acid cycle, regulates glycolytic and gluconeogenesis pathways, and improves the levels of sex hormones and energy metabolism. The intervention effects on the metabolic pathways were different between patients receiving combination therapy and patients receiving acupuncture therapy alone, suggesting that the dominant modulatory effect of Western drugs may largely conceal the efficacy of acupuncture intervention.

Feasibility of Investigational Procedures and Efficacy of a Personalized Omega-3 Dietary Intervention in Alleviating Pain and Psychoneurological Symptoms in Breast Cancer Survivors.

BACKGROUND: Breast cancer survivors (BCS) are at risk for psychoneurological symptoms (PNS) and inflammation for years following cancer treatment. Fish, particularly salmon, provides a rich source of omega-3 long chain fatty acids (omega-3LC), which has an anti-inflammatory effect. However, the benefit of omega-3LC on PNS is not well-known. AIMS: This study evaluated the feasibility and the initial efficacy of a personalized meal plan with dietary omega-3LC in reducing PNS. METHODS: A prospective, randomized controlled trial design (n = 46) was used to evaluate the feasibility of a personalized meal plan using two omega-3LC dose levels (high and low omega-3LC) in reducing PNS including pain, depression, fatigue, sleep, and stress. RESULTS: The recruitment rate was 4.9% with overall retention rate of 74% and 67.1% adherence to personalized meal plan and dietary procedures. Of participants who completed the investigation, 94% completed fish adherence logs and consumed ≥70% of the assigned quantity of fish. Saliva collection was 97.8% at baseline and 100% at follow-up. BCS in the high omega-3LC group had a significant decrease in pain (p < .01), perceived stress (p < .05), sleep (p < .001), depression (p < .001), and fatigue (p < .01) over the course of intervention. There were trends of PNS improvement in the low omega-3LC group but the differences did not reach statistical significance. CONCLUSION: Our results support the feasibility of our investigational design, procedures, and intervention. The outcomes provide preliminary support for an expanded research effort using fish as a source of omega-3LC and personalized dietary planning as a vehicle for symptom self-management in BCS.

Axial Load Measurement of Bolts with Different Clamping Lengths Based on High-Frequency Ultrasonic ZnO Film Sensor.

The ultrasonic testing method has been widely used for measuring the axial load of bolts. However, systematic calibrations are prerequisite if specific bolts have different clamping length configurations, which leads to low efficiency and measurement errors. The focus of this work was to measure the axial load of bolts with different clamping lengths by proposing a method of clamping length correction based on piezoelectric films in order to avoid the complicated calibration steps. Firstly, the relationship between longitudinal wave time-of-flight (TOF) and axial load under different clamping lengths was studied to correct the difference between the effective stress length and the actual clamping length. Secondly, the high-frequency ZnO piezoelectric film sensor was fabricated on the bolts to improve the accuracy of longitudinal wave TOF measurement. The results showed that the center frequency of the fabricated ultrasonic sensor reached 25 MHz, which could realize the high precision measurement of TOF. The proposed correction model proved to be effective for decreasing the measurement error below 2.7% in this experiment. In conclusion, the proposed method simplified the calibration procedure for different application configurations of the same bolt and realized the efficient measurement of bolt axial load.

Baseline Gut Microbiome Signatures Correlate with Immunogenicity of SARS-CoV-2 mRNA Vaccines.

The powerful immune responses elicited by the mRNA vaccines targeting the SARS-CoV-2 Spike protein contribute to their high efficacy. Yet, their efficacy can vary greatly between individuals. For vaccines not based on mRNA, cumulative evidence suggests that differences in the composition of the gut microbiome, which impact vaccine immunogenicity, are some of the factors that contribute to variations in efficacy. However, it is unclear if the microbiome impacts the novel mode of immunogenicity of the SARS-CoV-2 mRNA vaccines. We conducted a prospective longitudinal cohort study of individuals receiving SARS-CoV-2 mRNA vaccines where we measured levels of anti-Spike IgG and characterized microbiome composition, at pre-vaccination (baseline), and one week following the first and second immunizations. While we found that microbial diversity at all timepoints correlated with final IgG levels, only at baseline did microbial composition and predicted function correlate with vaccine immunogenicity. Specifically, the phylum Desulfobacterota and genus Bilophila, producers of immunostimulatory LPS, positively correlated with IgG, while Bacteroides was negatively correlated. KEGG predicted pathways relating to SCFA metabolism and sulfur metabolism, as well as structural components such as flagellin and capsular polysaccharides, also positively correlated with IgG levels. Consistent with these findings, depleting the microbiome with antibiotics reduced the immunogenicity of the BNT162b2 vaccine in mice. These findings suggest that gut microbiome composition impacts the immunogenicity of the SARS-CoV-2 mRNA vaccines.

Pain self-management plus activity tracking and nurse-led support in adults with chronic low back pain: feasibility and acceptability of the problem-solving pain to enhance living well (PROPEL) intervention.

BACKGROUND: Chronic low back pain can lead to individual suffering, high medical expenditures, and impaired social well-being. Although the role of physical activity in pain management is well established, the underlying mechanisms of biological and clinical outcomes are unknown. This study aimed to assess the feasibility and acceptability of a pain self-management intervention, Problem-Solving Pain to Enhance Living Well, which employs wearable activity tracking technology and nurse consultations for people with chronic low back pain. METHODS: This one-arm longitudinal study recruited 40 adults aged 18-60 years with chronic low back pain. Over 12 weeks, participants watched 10 short video modules, wore activity trackers, and participated in nurse consultations every 2 weeks. At baseline and the 12-week follow-up, they completed study questionnaires, quantitative sensory testing, and blood sample collection. RESULTS: Forty participants were recruited, and their mean age was 29.8. Thirty-two participants completed the survey questionnaire, quantitative sensory testing, Fitbit activity tracker, and bi-weekly nurse consultation, and 25 completed the evaluation of biological markers. The overall satisfaction with the Problem-Solving Pain to Enhance Living Well video modules, nurse consultations, and Fitbit in pain management was rated as excellent. No adverse events were reported. Between the baseline and 12-week follow-up, there was a significant decrease in pain intensity and interference and an increase in the warm detection threshold at the pain site. CONCLUSIONS: Despite concerns about the participant burden due to multidimensional assessment and intensive education, the feasibility of the Problem-Solving Pain to Enhance Living Well intervention was favorable. Technology-based self-management interventions can offer personalized strategies by integrating pain phenotypes, genetic markers, and physical activity types affecting pain conditions. TRIAL REGISTRATION: This pilot study was registered with ClinicalTrials.gov [NCT03637998, August 20, 2018]. The first participant was enrolled on September 21, 2018.

Associations of Mitochondrial Function, Stress, and Neurodevelopmental Outcomes in Early Life: A Systematic Review.

Early life stress is commonly experienced by infants, especially preterm infants, and may impact their neurodevelopmental outcomes in their early and later lives. Mitochondrial function/dysfunction may play an important role underlying the linkage of prenatal and postnatal stress and neurodevelopmental outcomes in infants. This review aimed to provide insights on the relationship between early life stress and neurodevelopment and the mechanisms of mitochondrial function/dysfunction that contribute to the neuropathology of stress. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to develop this systematic review. PubMed, Scopus, PsycINFO, and Biosis databases were searched for primary research articles published between 2010 and 2021 that examined the relationships among mitochondrial function/dysfunction, infant stress, and neurodevelopment. Thirty studies were identified. There is evidence to support that mitochondrial function/dysfunction mediates the relationship between prenatal and postnatal stress and neurodevelopmental outcomes in infants. Maternal transgenerational transmission of mitochondrial bioenergetic patterns influenced prenatal stress induced neurodevelopmental outcomes and behavioral changes in infants. Multiple functionally relevant mitochondrial proteins, genes, and polymorphisms were associated with stress exposure. This is the first review of the role that mitochondrial function/dysfunction plays in the association between stress and neurodevelopmental outcomes in full-term and preterm infants. Although multiple limitations were found based on the lack of data on the influence of biological sex, and due to invasive sampling, and lack of longitudinal data, many genes and proteins associated with mitochondrial function/dysfunction were found to influence neurodevelopmental outcomes in the early life of infants.

COVID-19 mRNA vaccine BNT162b2 induces autoantibodies against type I interferons in a healthy woman.

Coronavirus disease (COVID-19) caused by SARS-CoV-2 virus is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production in a small subset of patients. Pre-exiting neutralizing autoantibodies against type I interferons (IFNs) are associated with COVID-19 disease severity. In this case report, plasma levels of IgG against type I interferons (IFNs) were increased specifically among the 103 autoantibodies tested following the second shot of COVID-19 vaccine BNT162b2 compared to pre-vaccination and further increased following the third shot of BNT162b2 in a healthy woman. Unlike COVID-19 mediated autoimmune responses, vaccination in this healthy woman did not induce autoantibodies against autoantigens associated with autoimmune diseases. Importantly, IFN-α-2a-induced STAT1 responses in human PBMCs in vitro were suppressed by adding plasma samples from the study subject post- but not pre-vaccination. After the second dose of vaccine, the study subject exhibited severe dermatitis for about six months and responded to treatments with Betamethasone Dipropionate Ointment and antihistamines for about one month. Immune responses to type I IFN can be double-edged swords in enhancing vaccine efficacy and immune responses to infectious diseases, as well as accelerating chronic disease pathogenesis (e.g., chronic viral infections and autoimmune diseases). This case highlights the BNT162b2-induced neutralizing anti-type I IFN autoantibody production, which may affect immune functions in a small subset of general population and patients with some chronic diseases.

Efficient and risk-reduced genome editing using double nicks enhanced by bacterial recombination factors in multiple species.

Site-specific DNA double-strand breaks have been used to generate knock-in through the homology-dependent or -independent pathway. However, low efficiency and accompanying negative impacts such as undesirable indels or tumorigenic potential remain problematic. In this study, we present an enhanced reduced-risk genome editing strategy we named as NEO, which used either site-specific trans or cis double-nicking facilitated by four bacterial recombination factors (RecOFAR). In comparison to currently available approaches, NEO achieved higher knock-in (KI) germline transmission frequency (improving from zero to up to 10% efficiency with an average of 5-fold improvement for 8 loci) and 'cleaner' knock-in of long DNA fragments (up to 5.5 kb) into a variety of genome regions in zebrafish, mice and rats. Furthermore, NEO yielded up to 50% knock-in in monkey embryos and 20% relative integration efficiency in non-dividing primary human peripheral blood lymphocytes (hPBLCs). Remarkably, both on-target and off-target indels were effectively suppressed by NEO. NEO may also be used to introduce low-risk unrestricted point mutations effectively and precisely. Therefore, by balancing efficiency with safety and quality, the NEO method reported here shows substantial potential and improves the in vivo gene-editing strategies that have recently been developed.

Efficacy and safety of camrelizumab plus apatinib compared to apatinib monotherapy as third-line or above therapy for metastatic colorectal cancer patients: A retrospective cohort study.

WHAT IS KNOWN AND OBJECTIVE: Programmed cell death protein-1 (PD-1) inhibitors synergize apatinib for anti-tumour effect by regulating tumour microenvironment, vascular endothelial growth factor, hypoxia condition, immune response, etc. This study aimed to investigate the treatment efficacy and safety of camrelizumab (PD-1 inhibitor) plus apatinib as third-line or above therapy in metastatic colorectal cancer (mCRC) patients. METHODS: Totally, 64 unresectable mCRC patients receiving camrelizumab plus apatinib (N = 31) and apatinib (N = 33) were retrospectively enrolled. RESULTS: Disease control rate (80.6% vs. 57.6%) (P = 0.047) was elevated in camrelizumab plus apatinib group compared to apatinib group; however, objective response rate (22.6% vs. 6.1%) (P = 0.078) only showed an increasing trend but did not achieve statistical significance. Besides, the median (95% confidence interval [CI]) progressive-free survival (PFS) and overall survival (OS) were 6.9 (3.7-10.1) and 11.5 (7.7-15.3) months in camrelizumab plus apatinib group; meanwhile, the median (95% CI) PFS and OS were 3.6 (1.7-5.5) and 6.7 (5.0-8.4) months in the apatinib group. Additionally, PFS (P = 0.017) and OS (P = 0.006) were prolonged in camrelizumab plus apatinib group compared with apatinib group, which was confirmed by further multivariate Cox's proportional hazards regression analysis (hazard ratio [HR] = 0.340, P < 0.001 for PFS; HR = 0.271, P < 0.001 for OS). The incidence of total, grade 1-2, and grade 3-4 adverse events did not differ between groups (all P > 0.05). CONCLUSION: Camrelizumab (PD-1 inhibitor) plus apatinib achieves a better treatment efficacy than apatinib as third-line or above therapy with a good safety profile in mCRC patients.

Psychosocial and Sensory Factors Contribute to Self-Reported Pain and Quality of Life in Young Adults with Irritable Bowel Syndrome.

AIMS: Psychosocial and sensory factors, including anxiety, depression, and pressure pain threshold have been used to cluster chronic symptoms in irritable bowel syndrome (IBS). This study examined the contribution of psychosocial sensory factors on pain interference and quality of life (QOL) in this population. DESIGN: We performed a cross-sectional analysis of baseline data from a randomized controlled trial. SETTINGS: Two gastrointestinal clinics, general communities, and two large campuses of a public university in the Northeastern United States. PARTICIPANTS/SUBJECTS: Eighty young adults with IBS aged 21 ± 2.57 years (76.25% female). METHODS: Demographic and psychosocial factors including anxiety, depression, fatigue, cognition or general concerns, sleep disturbance, self-efficacy, coping, and food intake were measured as independent variables. Quantitative sensory testing was conducted to measure mechanical, thermal, and pressure pain thresholds. Self-reported pain measured by the brief pain inventory (BPI) and IBS-QOL were assessed as the outcome variables. Regression analysis and mediation analysis were conducted to determine the associated factors of IBS pain and QOL. RESULTS: Age, sex, and psychosocial factors including coping, self-efficacy, alcohol intake, mechanical pain sensitivity, and cold pain threshold were significantly associated with pain interference (all p < 0.05). Coping, and self-efficacy were significantly associated with IBS-QOL (all p < 0.05). In the mediation analysis, coping catastrophizing and self-efficacy were indirectly associated with IBS-QOL mediated by fatigue. CONCLUSIONS: Psychosocial factors including coping and self-efficacy, and quantitative sensory testing factors significantly correlate with self-reported pain and QOL among young adults with IBS. This preliminary research calls for further interventional studies that target personalized psychosocial and quantitative sensory factors to improve pain management and quality of life in IBS patients.

Self-Efficacy Survey Study of Pain Self-Management in Patients with Cancer.

BACKGROUND: Cancer pain prevalence remains high, and variance in self-efficacy for managing pain may explain why some patients experience greater pain severity. AIM: This study explored perceptions of self-efficacy in relation to cancer pain severity and treatment related characteristics. METHOD: A descriptive cross-sectional survey was administered to 50 cancer outpatients. Data analysis involved descriptive and correlational statistical analyses. RESULTS: Self-efficacy to manage pain was significantly associated with time since diagnosis and ability to deal with frustration, and inversely associated with pain severity level. A large proportion of patients reported low satisfaction self-managing their pain. Most patients reported independently self-managing their cancer pain; however, satisfaction with pain management was low for a large proportion of patients. Time since cancer diagnosis and ability to deal with frustration due to cancer pain were positively associated with cancer pain self-efficacy, whereas pain self-efficacy had a significant inverse correlation with cancer pain severity. CONCLUSIONS: Enhancing self-efficacy to self-manage under-treated cancer pain is important with implications for improving pain outcomes and quality of life. Further investigation on unmet needs and preferences for cancer pain self-management support is warranted.

Biochar induced improvement in root system architecture enhances nutrient assimilation by cotton plant seedlings.

BACKGROUND: Raising nitrogen use efficiency of crops by improving root system architecture is highly essential not only to reduce costs of agricultural production but also to mitigate climate change. The physiological mechanisms of how biochar affects nitrogen assimilation by crop seedlings have not been well elucidated. RESULTS: Here, we report changes in root system architecture, activities of the key enzymes involved in nitrogen assimilation, and cytokinin (CTK) at the seedling stage of cotton with reduced urea usage and biochar application at different soil layers (0-10 cm and 10-20 cm). Active root absorption area, fresh weight, and nitrogen agronomic efficiency increased significantly when urea usage was reduced by 25% and biochar was applied in the surface soil layer. Glutamine oxoglutarate amino transferase (GOGAT) activity was closely related to the application depth of urea/biochar, and it increased when urea/biochar was applied in the 0-10 cm layer. Glutamic-pyruvic transaminase activity (GPT) increased significantly as well. Nitrate reductase (NR) activity was stimulated by CTK in the very fine roots but inhibited in the fine roots. In addition, AMT1;1, gdh3, and gdh2 were significantly up-regulated in the very fine roots when urea usage was reduced by 25% and biochar was applied. CONCLUSION: Nitrogen assimilation efficiency was significantly affected when urea usage was reduced by 25% and biochar was applied in the surface soil layer at the seedling stage of cotton. The co-expression of gdh3 and gdh2 in the fine roots increased nitrogen agronomic efficiency. The synergistic expression of the ammonium transporter gene and gdh3 suggests that biochar may be beneficial to amino acid metabolism.

Hydrothermal-Induced Formation of Well-Defined Hollow Carbons with Curvature-Activated N-C Sites for Zn-Air Batteries.

Metal-free carbons have been regarded as one of the promising materials alternatives to precious-metal catalysts for oxygen reduction reaction (ORR) due to their high activity and stability. In this paper, well-defined N-doped hollow carbons (NHCs) are firstly synthesized by using an ammonia-based hydrothermal synthesis that is environmentally friendly and suitable for mass production in industry and a commercial black carbon as raw material. Moreover, the shell thickness of the NHCs can be easily tuned by this hydrothermal strategy. Zn-air battery test results reveal shell thickness-dependent activity and durability for ORR over the NHCs, which exceeds that obtained by commercial Pt/C (20 wt %). The enhanced battery performance can be attributed to the curvature-activated N-C moieties on the hollow carbon surface, which served as the main active sites for ORR as evidenced by DFT calculations. The proposed approach may open a way for designing curved hollow carbons with high graphitization degree and dopant nitrogen level for metal-air batteries or fuel cells.