Glycated Albumin and Adverse Clinical Outcomes in Patients With CKD: A Prospective Cohort Study.

RATIONALE & OBJECTIVE: Hemoglobin A1c (HbA1c) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,110 participants with CKD from the Chronic Renal Insufficiency Cohort study. EXPOSURE: Baseline GA levels. OUTCOME: Incident end-stage kidney disease (ESKD), cardiovascular disease (CVD) events, and all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards regression. RESULTS: Participant characteristics included mean age 59.0±10.8 SD years; 1,357 (43.6%) female; and 1,550 (49.8%) with diabetes. The median GA was 18.7% (IQR, 15.8%-23.3%). During an average 7.9-year follow-up, there were 980 ESKD events, 968 CVD events, and 1,084 deaths. Higher GA levels were associated with greater risks of all outcomes, regardless of diabetes status: hazard ratios for ESKD, CVD, and death among participants with the highest quartile compared with quartile 2 (reference) were 1.42 (95% CI, 1.19-1.69), 1.67 (95% CI, 1.39-2.01), and 1.63 (95% CI, 1.37-1.94), respectively. The associations with CVD and death appeared J-shaped, with increased risk also seen at the lowest GA levels. Among patients with coexisting CKD and diabetes, the associations of GA with outcomes remained significant even after adjusting for HbA1c. For each outcome, we observed a significant increase in the fraction of new prognostic information when both GA and HbA1c were added to models. LIMITATIONS: Lack of longitudinal GA measurements; and HbA1c measurements were largely unavailable in participants without diabetes. CONCLUSIONS: Among patients with CKD, GA levels were independently associated with risks of ESKD, CVD, and mortality, regardless of diabetes status. GA added prognostic value to HbA1c among patients with coexisting CKD and diabetes. PLAIN-LANGUAGE SUMMARY: Hemoglobin A1c (HbA1c) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown. In this cohort study of 3,110 individuals with non-dialysis-dependent CKD, GA levels were independently associated with risks of end-stage kidney disease, cardiovascular disease (CVD), and mortality. The associations with CVD and mortality appeared to be J-shaped. Among patients with coexisting CKD and diabetes, GA added prognostic value to HbA1c. Thus, GA may be a valuable complementary test to HbA1c in patients with CKD.

Combination anlotinib and toripalimab for an advanced biliary tract cancer patient with high Eastern Cooperative Oncology Group performance status: a case report.

Up to 80% of biliary tract cancer (BTC) patients relapse within 3 years after surgery and the efficacy of second-line treatment remains dismal for patients who progressed on gemcitabine and cisplatin chemotherapy. Median overall survival of patients with palliative chemotherapy is less than 1 year. The feasibility and safety of targeted therapies plus immunotherapies remain scanty currently, and patients with recurrent or advanced BTCs often experience a rapid decline in Eastern Cooperative Oncology Group (ECOG) performance status. This case report is the first report suggesting a 17-month progression-free survival (PFS), partial response, and another 11-month PFS after progressive disease of anlotinib plus toripalimab in advanced BTC with high ECOG performance status. We report a 67-year-old Chinese male with BTC. He was observed with progressive disease after surgical resection, adjuvant chemotherapy, palliative chemotherapy, and diagnosed with American Joint Committee on Cancer clinical stage IV (cT3N0M1) extrahepatic BTC. The patient experienced a rapid decline in performance status, and he received oral anlotinib and toripalimab with informed consent. MRI scans showed partial response on 22 June 2022. PET-CT showed that tumor activity has been inhibited on 8 March 2023. He achieved 17 months of PFS. Although the patient developed solitary lung metastasis, he had a continuous survival benefit from treatment of anlotinib plus toripalimab after lung radiotherapy. Until the writing of the case draft, he had achieved another 11 months of PFS. The present case suggests that anlotinib plus toripalimab might be a potential effective treatment for advanced BTCs patients with high ECOG performance status.

Comparative CKD risk prediction using homocitrulline and carbamylated albumin: two circulating markers of protein carbamylation.

BACKGROUND: Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies. METHODS: Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2-4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker. RESULTS: Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35-2.66) for C-Alb, and 1.89 [1.27-2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10-1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707-0.743] with C-Alb and 0.725 [0.707-0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics. CONCLUSIONS: C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.

Protein Carbamylation and the Risk of ESKD in Patients with CKD.

SIGNIFICANCE STATEMENT: Protein carbamylation, a nonenzymatic post-translational protein modification partially driven by elevated blood urea levels, associates with mortality and adverse outcomes in patients with ESKD on dialysis. However, little is known about carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD. In this prospective observational cohort study of 3111 individuals with CKD stages 2-4, higher levels of carbamylated albumin (a marker of protein carbamylation burden) were associated with a greater risk of developing ESKD and other significant adverse clinical outcomes. These findings indicate that protein carbamylation is an independent risk factor for CKD progression. They suggest that further study of therapeutic interventions to prevent or reduce carbamylation is warranted. BACKGROUND: Protein carbamylation, a post-translational protein modification partially driven by elevated blood urea levels, associates with adverse outcomes in ESKD. However, little is known about protein carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD. METHODS: To test associations between protein carbamylation and the primary outcome of progression to ESKD, we measured baseline serum carbamylated albumin (C-Alb) in 3111 patients with CKD stages 2-4 enrolled in the prospective observational Chronic Renal Insufficiency Cohort study. RESULTS: The mean age of study participants was 59 years (SD 10.8); 1358 (43.7%) were female, and 1334 (42.9%) were White. The mean eGFR at the time of C-Alb assessment was 41.8 (16.4) ml/minute per 1.73 m 2 , and the median C-Alb value was 7.8 mmol/mol (interquartile range, 5.8-10.7). During an average of 7.9 (4.1) years of follow-up, 981 (31.5%) individuals developed ESKD. In multivariable adjusted Cox models, higher C-Alb (continuous or quartiles) independently associated with an increased risk of ESKD. For example, compared with quartile 1 (C-Alb ≤5.80 mmol/mol), those in quartile 4 (C-Alb >10.71 mmol/mol) had a greater risk for ESKD (adjusted hazard ratio, 2.29; 95% confidence interval, 1.75 to 2.99), and the ESKD incidence rate per 1000 patient-years increased from 15.7 to 88.5 from quartile 1 to quartile 4. The results remained significant across numerous subgroup analyses, when treating death as a competing event, and using different assessments of eGFR. CONCLUSIONS: Having a higher level of protein carbamylation as measured by circulating C-Alb is an independent risk factor for ESKD in individuals with CKD stages 2-4. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_04_24_JSN_URE_EP22_042423.mp3.

Realizing Low-Temperature Graphite-based Rechargeable Potassium-Ion Full Battery.

Graphite (Gr) has been considered as the most promising anode material for potassium-ion batteries (PIBs) commercialization due to its high theoretical specific capacity and low cost. However, Gr-based PIBs remain unfeasible at low temperature (LT), suffering from either poor kinetics based on conventional carbonate electrolytes or K+ -solvent co-intercalation issue based on typical ether electrolytes. Herein, a high-performance Gr-based LT rechargeable PIB is realized for the first time by electrolyte chemistry. Applying unidentate-ether-based molecule as the solvent dramatically weakens the K+ -solvent interactions and lowers corresponding K+ de-solvation kinetic barrier. Meanwhile, introduction of steric hindrance suppresses co-intercalation of K+ -solvent into Gr, greatly elevating operating voltage and cyclability of the full battery. Consequently, the as-prepared Gr||prepotassiated 3,4,9,10-perylene-tetracarboxylicacid-dianhydride (KPTCDA) full PIB can reversibly charge/discharge between -30 and 45 °C with a considerable energy density up to 197 Wh kgcathode -1 at -20 °C, hopefully facilitating the development of LT PIBs.

Hybrid Lamellar Superlattices with Monoatomic Platinum Layers and Programmable Organic Ligands.

Compared with layered materials such as graphite and transitional metal dichalcogenides with highly anisotropic in-plane covalent bonds, freestanding metallic two-dimensional (2D) films with atomic thickness are intrinsically more difficult to achieve. The omnidirectional nature of typical metallic bonds prevents the formation of highly anisotropic atomically thin metallic layers. Herein, we report a ligand regulation strategy to stabilize monoatomic platinum layers by forming a unique lamellar superlattice structure with self-assembled organic ligand layers. We show that the interlayer spacings and coordination environments could be systematically tuned by varying programmable molecular ligands with the designed length and structural motifs, which further modulate the electronic states and catalytic performances. The strategy can be extended for preparing lamellar superlattices with monoatomic metallic layers from silver and gold. Such general and delicate synthetic control provides an exciting model system for systematic investigation of the intriguing structure-property correlation of monoatomic layers and promises a molecular design pathway for heterogeneous catalysts.

Insights into Advanced Neurological Dysfunction Mechanisms Following DBS Surgery in Parkinson's Patients: Neuroinflammation and Pyroptosis.

Parkinson's disease is a severe neurodegenerative disorder. Currently, deep brain electrical stimulation (DBS) is the first line of surgical treatment. However, serious neurological impairments such as speech disorders, disturbances of consciousness, and depression after surgery limit the efficacy of treatment. In this review, we summarize the recent experimental and clinical studies that have explored the possible causes of neurological deficits after DBS. Furthermore, we tried to identify clues from oxidative stress and pathological changes in patients that could lead to the activation of microglia and astrocytes in DBS surgical injury. Notably, reliable evidence supports the idea that neuroinflammation is caused by microglia and astrocytes, which may contribute to caspase-1 pathway-mediated neuronal pyroptosis. Finally, existing drugs and treatments may partially ameliorate the loss of neurological function in patients following DBS surgery by exerting neuroprotective effects.

Palladium-catalyzed cascade cyclization of allenamide with 2-iodoanilines to access functionalized indoloquinolines.

A novel and efficient palladium-catalyzed cascade cyclization to indoloquinoline derivatives in one pot has been developed by using allenamide derivatives and 2-iodoanilines as the key building blocks. The process involved two cyclizations: intramolecular cyclization/π-allylic substitution and intramolecular 6-endo Heck cyclization. Furthermore, dihydrobenzofuro[2,3-b]quinoline derivatives could also be achieved via this strategy using allenyl ethers instead of allenamides. The readily available substrates, mild conditions, high efficiency and step economy make this strategy a promising method in the synthesis of polycyclic motifs.

Rechargeable Potassium-Ion Full Cells Operating at -40 °C.

Potassium-ion batteries (PIBs) are promising for cryogenic energy storage. However, current researches on low-temperature PIBs are limited to half cells utilizing potassium metal as an anode, and realizing rechargeable full cells is challenged by lacking viable anode materials and compatible electrolytes. Herein, a hard carbon (HC)-based low-temperature potassium-ion full cell is successfully fabricated for the first time. Experimental evidence and theoretical analysis revealed that potassium storage behaviors of HC anodes in the matched low-temperature electrolyte involve defect adsorption, interlayer co-intercalation, and nanopore filling. Notably, these unique potassiation processes exhibited low interfacial resistances and small reaction activation energies, enabling an excellent cycling performance of HC with a capacity of 175 mAh g-1 at -40 °C (68 % of its room-temperature capacity). Consequently, the HC-based full cells demonstrated impressive rechargeability and high energy density above 100 Wh kg-1 cathode at -40 °C, representing a significant advancement in the development of PIBs.

Elevated N-terminal pro C-type natriuretic peptide is associated with mortality in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Unlike N-terminal pro-B-type natriuretic peptide (NT-proBNP), which have been extensively studied, little is known about the role of N-terminal pro-C-type natriuretic peptide (NT-proCNP) for predicting survival post transcatheter aortic valve replacement (TAVR). METHODS: A total of 309 patients were included in the analysis. Patients were grouped into quartiles (Q1-4) according to the baseline NT-proCNP value. Blood for NT-proCNP analysis was obtained prior to TAVR procedure. The primary endpoint was mortality after a median follow-up of 32 months. Multivariable Cox proportional hazards regression models analyzed prognostic factors. The predictive capability was compared between NT-proBNP and NT-proCNP using receiver operator curve (ROC) analysis. RESULTS: A total of 309 subjects with the mean age of 76.8 ± 6.3 years, among whom 58.6% were male, were included in the analysis. A total of 58 (18.8%) patients died during follow-up. Cox multivariable analyses indicated society of thoracic surgeons (STS)-score was a strong independent predictor for mortality (hazard ratio (HR) 1.08, 95% confidential interval (CI) 1.05-1.12, P < 0.001). Elevated NT-proCNP was associated with a higher risk of cardiovascular mortality (HR 1.02, 95% CI 1.00-1.03, P = 0.025) and All-cause mortality (HR 1.01, 95% CI 1.00-1.03, P = 0.027), whereas NT-proBNP showed a small effect size on mortality. ROC analysis indicated that NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with left ventricular ejection fraction (LVEF) < 50% [(Area under the curve (AUC)-values of 0.79 (0.69; 0.87) vs. 0.59 (0.48; 0.69), P = 0.0453]. CONCLUSIONS: NT-proCNP and STS-Score were the independent prognostic factors of mortality among TAVR patients. Furthermore, NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with LVEF < 50%. Trial registration NCT02803294, 16/06/2016.

Screening of ulcerative colitis biomarkers and potential pathways based on weighted gene co-expression network, machine learning and ceRNA hypothesis.

BACKGROUND: Ulcerative colitis (UC) refers to an intractable intestinal inflammatory disease. Its increasing incidence rate imposes a huge burden on patients and society. The UC etiology has not been determined, so screening potential biomarkers is critical to preventing disease progression and selecting optimal therapeutic strategies more effectively. METHODS: The microarray datasets of intestinal mucosal biopsy of UC patients were selected from the GEO database, and integrated with R language to screen differentially expressed genes and draw proteins interaction network diagrams. GO, KEGG, DO and GSEA enrichment analyses were performed to explore their biological functions. Through machine learning and WGCNA analysis, targets that can be used as UC potential biomarkers are screened out. ROC curves were drawn to verify the reliability of the results and predicted the mechanism of marker genes from the aspects of immune cell infiltration, co-expression analysis, and competitive endogenous network (ceRNA). RESULTS: Two datasets GSE75214 and GSE87466 were integrated for screening, and a total of 107 differentially expressed genes were obtained. They were mainly related to biological functions such as humoral immune response and inflammatory response. Further screened out five marker genes, and found that they were associated with M0 macrophages, quiescent mast cells, M2 macrophages, and activated NK cells in terms of immune cell infiltration. The co-expression network found significant co-expression relationships between 54 miRNAs and 5 marker genes. According to the ceRNA hypothesis, NEAT1-miR-342-3p/miR-650-SLC6A14, NEAT1-miR-650-IRAK3, and XIST-miR-342-3p-IRAK3 axes were found as potential regulatory pathways in UC. CONCLUSION: This study screened out five biomarkers that can be used for the diagnosis and treatment of UC, namely SLC6A14, TIMP1, IRAK3, HMGCS2, and APOBEC3B. Confirmed that they play a role in the occurrence and development of UC at the level of immune infiltration, and proposed a potential RNA regulatory pathway that controls the progression of UC.

Internal nitrogen and phosphorus loading in a seasonally stratified reservoir: Implications for eutrophication management of deep-water ecosystems.

Water eutrophication is a serious global issue because of excess external and internal nutrient inputs. Understanding the intensity and contribution of internal nitrogen (N) and phosphorus (P) loading in deep-water ecosystems is of great significance for water body eutrophication management. In this study, we combined intact sediment core incubation, high-resolution peeper (HR-Peeper) sampling, and analysis of N and P forms and other environmental factors in the water column and sediments to evaluate the contributions of internal N and P loading to water eutrophication by N and P fluxes across the sediment-water interface (SWI) of the Panjiakou Reservoir (PJKR), a deep-water ecosystem where eutrophication threatens the security of the local drinking water supply in North China. The results indicated that the PJKR showed obvious thermal and dissolved oxygen (DO) stratification in the warm seasons and full mixing in the cold seasons. The mean DO concentration was 9.9 and 3.55 mg/L in the epilimnion and hypolimnion, respectively, in warm seasons and 10.7 mg/L in cold seasons. The sediment acted as a source of soluble reactive phosphorus (SRP), NH4+-N, and NO2--N and a sink of NO3--N. The SRP fluxes were 5.28 ± 4.34 and 2.30 ± 1.93 mg m-2·d-1 in warm and cold seasons, respectively, and the dissolved inorganic nitrogen (DIN) fluxes were -0.66 ± 47.84 and 44.04 ± 84.05 mg m-2·d-1. Seasonal hypoxia accelerated the release of P rather than N from the sediments in warm seasons, which came mainly from Fe-P and Org-P under anoxic conditions. The strong negative NO3--N flux (diffusion from the water column to the sediment) implied an intensive denitrification process at the SWI, which can counteract the release flux of NH4+-N and NO2--N, resulting in the sediment acting as a weak dissolved inorganic nitrogen (DIN) source for the overlying water. We also found that internal N loading accounted for only ∼9% of the total N loading, while internal P loading accounted for 43% of the total P loading of the reservoir. Our results highlight that efforts to manage the internal loading of deep-water ecosystems should focus on P and seasonal hypoxia.

Patterns and drivers of CH4 concentration and diffusive flux from a temperate river-reservoir system in North China.

Freshwater reservoirs are regarded as an important anthropogenic source of methane (CH4) emissions. The temporal and spatial variability of CH4 emissions from different reservoirs results in uncertainty in the estimation of the global CH4 budget. In this study, surface water CH4 concentrations were measured and diffusive CH4 fluxes were estimated via a thin boundary layer model in a temperate river-reservoir system in North China, using spatial (33 sites) and temporal (four seasons) monitoring; the system has experienced intensive aquaculture disturbance. Our results indicated that the dissolved CH4 concentration in the reservoir ranged from 0.07 to 0.58 µmol/L, with an annual average of 0.13 ± 0.10 µmol/L, and the diffusive CH4 flux across the water-air interface ranged from 0.66 to 3.61 µmol/(m2•hr), with an annual average of 1.67 ± 0.75 µmol/(m2•hr). During the study period, the dissolved CH4 concentration was supersaturated and was a net source of atmospheric CH4. Notably, CH4 concentration and diffusive flux portrayed large temporal and spatial heterogeneity. The river inflow zone was determined to be a hotspot for CH4 emissions, and its flux was significantly higher than that of the tributary and main basin; the CH4 flux in autumn was greater than that in other seasons. We also deduced that the CH4 concentration/diffusive flux was co-regulated mainly by water temperature, water depth, and water productivity (Chla, trophic status). Our results highlight the importance of considering the spatiotemporal variability of diffusive CH4 flux from temperate reservoirs to estimate the CH4 budget at regional and global scales.

Asymmetric Enamide-Imine Tautomerism in the Kinetic Resolution of Tertiary Alcohols.

An efficient protocol for kinetic resolution of tertiary alcohols has been developed through an unprecedented asymmetric enamide-imine tautomerism process enabled by chiral phosphoric acid catalysis. A broad range of racemic 2-arylsulfonamido tertiary allyl alcohols could be kinetically resolved with excellent kinetic resolution performances (with s-factor up to >200). This method is particularly effective for a series of 1,1-dialkyl substituted allyl alcohols, which produced chiral tertiary alcohols that would be difficult to access via other asymmetric methods. Facile and versatile transformations of the chiral α-hydroxy imine and enamide products, especially the efficient stereodivergent synthesis of all four stereoisomers of ß-amino tertiary alcohols using one enantiomer of the catalyst, demonstrated the value of this kinetic resolution method.

Rechargeable Aqueous Aluminum Organic Batteries.

Aqueous aluminum-ion batteries (AABs) are regarded as promising next-generation energy storage devices, and the current reported cathodes for AABs mainly focused on inorganic materials which usually implement a typical Al3+ ions (de)insertion mechanism. However, the strong electrostatic forces between Al3+ and the host materials usually lead to sluggish kinetics, poor reversibility and inferior cycling stability. Herein, we employ an organic compound with redox-active moieties, phenazine (PZ), as the cathode material in AABs. Different from conventional inorganic materials confined by limited lattice spacing and rigid structure, the flexible organic molecules allow a large-size Al-complex co-intercalation through reversible redox active centers (-C=N-) of PZ. This co-intercalation behavior can effectively reduce desolvation penalty, and substantially lower the Coulombic repulsion during the ion (de)insertion process. Consequently, this organic cathode exhibits a high capacity and excellent cyclability, which exceeds those of most reported electrode materials for AABs. This work highlights the anion co-intercalation chemistry of redox-active organic materials, which is expected to boost the development of high-performance multivalent-ion battery systems.

Chiral Phosphoric Acid Catalyzed Kinetic Resolution of 2-Amido Benzyl Alcohols: Asymmetric Synthesis of 4H-3,1-Benzoxazines.

An efficient method for the asymmetric synthesis of 4H-3,1-benzoxazines was developed by kinetic resolution of 2-amido benzyl alcohols using chiral phosphoric acid catalyzed intramolecular cyclizations. A broad range of benzyl alcohols (both secondary and tertiary alcohols) were kinetically resolved with high selectivities, with an s factor of up to 94. Mechanistic studies were performed to elucidate the mechanism of these reactions, wherein the amide moieties reacted as the electrophiles. Gram-scale reaction and facile transformations of the chiral products demonstrate the potential of this method in asymmetric synthesis of biologically active chiral heterocycles.

Role of neuromedin B and its receptor in the innate immune responses against influenza A virus infection in vitro and in vivo.

The peptide neuromedin B (NMB) and its receptor (NMBR) represent a system (NMB/NMBR) of neuromodulation. Here, it was demonstrated that the expression of NMBR in cells or murine lung tissues was clearly upregulated in response to H1N1/PR8 influenza A virus infection. Furthermore, the in vitro and in vivo activities of NMB/NMBR during PR8 infection were investigated. It was observed that A549 cells lacking endogenous NMBR were more susceptible to virus infection than control cells, as evidenced by the increased virus production in the cells. Interestingly, a significant decrease in IFN-α and increased IL-6 expression were observed in these cells. The role of this system in innate immunity against PR8 infection was probed by treating mice with NMB. The NMB-treated mice were less susceptible to virus challenge, as evidenced by increased survival, increased body weight, and decreased viral NP expression compared with the control animals. Additionally, the results showed that exogenous NMB not only enhanced IFN-α expression but also appeared to inhibit the expression of NP and IL-6 in PR8-infected cells and animals. As expected, opposing effects were observed in the NMBR antagonist-treated cells and mice, which further confirmed the effects of NMB. Together, these data suggest that NMB/NMBR may be an important component of the host defence against influenza A virus infection. Thus, these proteins may serve as promising candidates for the development of novel antiviral drugs.

Dietary carbohydrate intake, glycaemic index, glycaemic load and digestive system cancers: an updated dose-response meta-analysis.

Several studies analysed the associations between dietary carbohydrate intake, glycaemic index (GI) and glycaemic load (GL) and digestive system cancers; however, the results remain controversial. This study was to perform a meta-analysis evaluating the quantitative and dose-response associations between carbohydrate intake, GI and GL, and risk of digestive system cancers. We searched medical and biological databases up to June 2018 and identified twenty-six cohort studies and eighteen case-control studies. Meta-analytic fixed or random effects models were applied to process data. We also performed dose-response analysis, meta-regression and subgroup analyses. We found that high levels of GI were significantly associated with the risk of digestive system cancers at the highest compared with the lowest categories from cohort studies (summary relative risk (RR)=1·10, 95 % CI 1·05, 1·15). Similar effects were observed from case-control studies of the comparison between the extreme categories, but the difference did not reach statistical significance (summary OR=1·28, 95 % CI 0·97, 1·69). We also observed significant dose-response association between GI and digestive system cancers, with every 10-unit increase in GI (summary RR=1·003; 95 % CI 1·000, 1·012 for cohort studies; summary OR=1·09; 95 % CI 1·06, 1·11 for case-control studies). In addition, both cohort studies and case-control studies indicated that neither dietary carbohydrate intake nor GL bore any statistical relationship to digestive system cancers from the results of the highest compared with the lowest categories analyses and dose-response analyses. The results suggest a moderate association between high-GI diets and the risk of digestive system cancers.