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Fargesia nitida is a cold-resistant evergreen bamboo and is a pioneer plant in the secondary succession after the native trees were destroyed in the eastern Tibetan Plateau. However, little is known about the effects of this plant on soil conditions and about its microbiomes. Aiming at learning the interactions among the soil characteristics, the plants and the microbes in relation to the plant succession, a study on cultivated microbes associated with the rhizocompartments of F. nitida was performed in the present study to reveal the preference of this plant to the root associated microbes, in comparison with that associated with the successive spruce (Picea asperata Mast.) trees. The results demonstrated that growth of F. nitida could improve the soil nutrient contents, especially increasing total nitrogen, NH4+-N, total carbon, and microbial biomass carbon, and maintained more soil bacteria than the successive spruce trees. Based upon the study of F. nitida root-associated cultivated microbial community, the nutrient improvement in F. nitida growing soils might be from the root endophytic bacteria, which presented greater abundance (3.8, 1.7, and 12.6 folds) than that of bacteria in its rhizosphere, root zone soil, and spruce root zone soil, respectively. Pseudomonas members, especially species related to P. baetica and P. vancouverensis, were strongly selected by F. nitida as root endophytes.

We aim to explore the effect of head-down position (HDP), initiated within 24 hours of onset, in moderate anterior circulation stroke patients with probable large artery atherosclerosis (LAA) etiology. This investigator-initiated, multi-center trial prospective, randomized, open-label, blinded-endpoint, multi-center and phase-2 trial was conducted in China and completed in 2021. Eligible patients were randomly assigned (1:1) into the HDP group receiving −20° Trendelenburg, or control group receiving standard care according to national guideline. The primary endpoint was proportion of modified Rankin Scale (mRS) of 0 to 2 at 90 days, which is a scale for measuring the degree of disability after stroke. 90-day mRS was assessed by a certified staff member who was blinded to group assignment. A total of 96 patients were randomized (47 in HDP group and 49 in control group) and 94 (97.9%) patients were included in the final analysis: 46 in HDP group and 48 in control group. The proportion of favorable outcome was 65.2% (30/46) in the HDP group versus 50.0% (24/48) in the control group (unadjusted: OR 2.05 [95%CI 0.87-4.82], P = 0.099). No severe adverse event was attributed to HDP procedures. This work suggests that the head-down position seems safe and feasible, but does not improve favorable functional outcome in acute moderate stroke patients with LAA. This trial was registered with ClinicalTrials.gov, NCT03744533.

Background: Several studies performed thus far indicate that neuroinflammation may be one of the mechanisms underlying the pathogenesis of neuropathic pain (NP). Autophagy, as an adaptive response, has been regarded as an active process of removing the inflammatory stimulus and restoring homeostatic balance. Resolution of inflammation is a biochemical process mediated by the so-called aspirin-triggered specialized proresolving lipid mediators (AT-SPMs), which are thought to exert protective effects in NP. Recent studies have proposed mechanisms in models of inflammatory disorders and showed a relationship between resolution of inflammation and autophagy. This study aimed to validate the functional effects of Aspirin-triggered Resolvin D1 (AT-RvD1) on in vitro and in vivo models of inflammation and to determine their roles in the regulation of autophagy and activation of the Nod-like receptor protein 3 (NLRP3) inflammasome signaling pathway.Methods: An NP model was established using L5-6 spinal nerve ligation (SNL) and a model of tumor necrosis factor alpha (TNF-α)-stimulated primary microglia was established to evaluate the effect of SPMs. Western blotting was used to detect the level of NLRP3 inflammasomes complexes proteins (NLRP3, ASC, and Caspase-1) and autophagy-related proteins (LC3B, and Beclin1). Immunofluorescence staining was used to understand the autophagy and NLRP3 inflammasome activation process. The behavioral changes in rats were analyzed using paw withdrawal thresholds (PWT) and paw withdrawal latency (PWL) test.Results: Our results showed that AT-SPMs significantly upregulated the activation of autophagy, which was characterized by an increase in the ratio of LC3B-II/I and accumulation of ATG5 and Beclin1. AT-RvD1 showed a dose-dependent decrease in the upregulated PWT and PWL induced by SNL and suppressed the expression of the NLRP3 inflammasome protein and the production of its corresponding downstream proinflammatory factors. Additionally, AT-RvD1 induced the activation of autophagy of the microglia and decreased the expression of the NLRP3 inflammasome protein and the accumulation of proinflammatory factors in TNF-ɑ-challenged microglia.Conclusion: Thus, these results showed that AT-RvD1 may be a potential alternative therapeutic strategy for the prevention or treatment of NP by inhibition of the NLRP3 inflammasome signaling pathway by targeting the induction of autophagy.

An electrostatic lattice is composed of many micro-scale traps. It is a powerful tool for manipulating cold polar molecules on a chip with the help of the interaction between the dipole moment and the inhomogeneous electric field. To the best of our knowledge, the existing electrostatic lattice still suffers the nonadiabatic transition that will lead to the escape of molecules from the electrostatic trap. In the paper, we skillfully design the electrode structure to avoid the zero-field zone at the center of every single microtrap, and the nonadiabatic transitions can be prevented. First, we numerically calculate the distribution of the spatial electrostatic field. Then, the influences of voltages on the electric field intensity and the height of the trap center are investigated. We simulate of the trajectory of molecules using the Monte Carlo method and figure out the factors impacting the loading efficiency of our electrostatic lattice. At last, we discuss how the voltages and the loading positions affect the positional distribution of trapped molecules.

Tea polysaccharides have gained great attention but acid-assisted extraction was scarcely studied. Herein, an acid-extracted tea polysaccharide TP-1 was isolated. TP-1 contained glucose and galactose in a molar ratio of 4.33:1.00, and the molecular weight was 9.47 × 103 Da. The backbone is comprised of 1,4-α-Glcp, 1,6-α-Glcp, and 1,4-β-Galp, with branches of 1,4,6-α-Glcp. Polysaccharide TP-1 could scavenge DPPH, hydroxyl, and superoxide radicals, with the IC50 value of 457.1, 516.5, and 620.1 µg/mL, respectively. Furthermore, it could inhibit α-glucosidase and α-amylase activities with the IC50 value of 394.3 and 90.1 µg/mL, respectively. Meanwhile, glucose uptake was also observed to be significantly increased in insulin-resistant 3T3-L1 cells by TP-1. The results demonstrated that TP-1 might be employed for the control of diabetes mellitus.

Background Nocebo effect is prevalent among neurological diseases, resulting in low adherence and treatment outcome. We sought to examine the nocebo effect in randomized controlled trials (RCTs) in multiple system atrophy (MSA). Methods We searched RCTs in MSA from Medline since September, 2021. RCTs for drug treatment conducted in adult MSA patients with more than 5 cases in each treatment arm were included. We assessed the number of dropout due to placebo intolerance. We also did a symptomatic/disease-modifying subgroup analysis based on two different treatment purposes. The STATA software was used for statistical analysis. Overall heterogeneity was assessed using the Cochran Q and I2. Results Data were extracted from 11 RCTs fulfilling our search criteria. Of 540 placebo-treated patients, 64.2% reported at least one adverse event (AE) and 7.5% reported dropout because of AEs. The chance of dropping out because of an AE and experiencing at least one AE did not differ between placebo and active drug treatment arms. Besides, the pooled nocebo dropout rate in the symptomatic subgroup was similar to that of the disease-modifying subgroup. Conclusion In MSA RCTs, nocebo dropout rate was not at a low level among neurological disorders. Nocebo effect was an important reason of dropout because of AE in placebo and active drug treatment arms. Different treatment purposes may not influence nocebo effect.

Collateral therapeutics exert a promising protective effect on the outcome of acute ischemic stroke. Cerebral blood flow (CBF) may be modulated by different head positioning. The current study aimed to determine the effect of head-down tilt (HDT) on stroke in a rodent model.The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was used in this study. Neurological deficit scoring, 2,3,5-triphenyltetrazolium chloride staining, brain water content, perivascular aquaporin protein-4 (AQP4) localization, pericyte marker platelet-derived growth factor receptor β (PDGFRβ), and CBF velocity were evaluated at 24 h after MCAO/R and HDT treatment.In the rat model of MCAO/R, brain infarct volume and neurological deficit score were significantly alleviated in the -30° and -60° groups compared to those in the lying flat (0°) group. Compared with the 0° group, an increase in CBF velocity was detected in the -30° group through two-photon microscopy imaging at 24 h after MCAO/R. Compared with the SHAM group, a decrease in PDGFRβ was observed in both the MCAO/R and HDT treatment (-30°) groups. The integrated optical density of PDGFRβ was found to be higher in the HDT treatment (-30°) group than in the MCAO/R group. An impairment in perivascular AQP4 polarity and an increase in brain water content were observed after MCAO/R, which were not exacerbated by HDT treatment (-30°).Our findings suggest that HDT treatment at certain degrees may exert a neuroprotective effect after MCAO/R through improving CBF velocity and the protection of pericytes.

In microglia, Toll-like receptor 4 (TLR4) is well known to contribute to neuroinflammatory responses following brain ischemia. Meanwhile, TLR4 is also expressed in neurons and can mediate the conduction of calcium (Ca2+) influx, but the mechanistic link between neuronal TLR4 signaling and brain ischemic injury is still poorly understood. Here, primary neuronal cell culture from TLR4 knockout mice and conditional knockout mice of TLR4 in glutamatergic neurons (TLR4cKO) were used to establish ischemic models in vitro and in vivo, respectively. We found that deleting TLR4 reduced the neuronal death and intracellular Ca2+ increase induced by oxygen and glucose deprivation (OGD) or lipopolysaccharide treatment. Infarct volume and functional deficits also were alleviated in TLR4cKO mice following cerebral ischemia/reperfusion (I/R). Furthermore, TLR4 and N-methyl-d-aspartate receptor subunit 2B (NMDAR2B) were colocalized in neurons. Deleting TLR4 in neurons rescued phosphorylates NMDAR2B up-regulation induced by ischemia via Src kinase in vitro and in vivo. Downstream signaling of NMDAR2B, the interaction of neuronal nitric oxide synthase (nNOS) with postsynaptic density protein-95 (PSD-95) also was disrupted in TLR4cKO mice following cerebral I/R. Taken together, we described a novel molecular neuronal pathway that TLR4 signal in neurons play a crucial role in the neuronal death, and provided a new target for neuroprotection after ischemic stroke.

Ischemic preconditioning (IPC) could protect the blood-brain barrier (BBB), but the underlying mechanism is not well understood. This preclinical study aimed to investigate whether glycocalyx could be involved in the neuroprotective effect of IPC on cerebral ischemia-reperfusion injury (IRI) and the possible mechanism in rat middle cerebral artery occlusion/reperfusion (MCAO/R) model. Neurological deficit scores, infarct volume, and brain edema were measured to assess the neuroprotection of IPC. Several serum biomarkers related to glycocalyx damage, such as hyaluronic acid (HA), heparan sulfate (HS), and syndecan-1 (SYND1), were evaluated, and their changes were normalized to the ratio of postoperative/preoperative concentration. Western blot and immunofluorescence were used to evaluate the content and cellular location of HA-related metabolic enzymes. This study found that (1) IPC improved brain infarction and edema, neurological impairment, and BBB disruption in IRI rats; (2) IPC significantly up-regulated HA ratio and down-regulated HS ratio, but did not affect SYND1 ratio compared with the IRI group. Moreover, the increased HA ratio was negatively related to brain edema and neurological deficit score. (3) IPC affected HA metabolism by up-regulating hyaluronate synthase-1 and matrix metalloproteinase-2, and down-regulating hyaluronidase-1 in brain tissue. Together, this is the first report that the neuroprotective effect of IPC on IRI may be mediated through interfering with glycocalyx in the MCAO/R model.

Background: Human amniotic epithelial cells (hAECs) are seed cells used to treat acute myocardial infarction (AMI), but their mechanism remains unclear. Methods: We cultured hAECs and extracted exosomes from culture supernatants. Next, we established a stable AMI model in rats and treated them with hAECs, exosomes, or PBS. We assess cardiac function after treatment by echocardiography. Additionally, heart tissues were collected and analyzed by Masson’s trichrome staining. We conducted the tube formation and apoptosis assays to explore the potential mechanisms. Results: Cardiac function was improved, and tissue fibrosis was decreased following implantation of hAECs and their exosomes. Echocardiography showed that the EF and FS were lower in the control group than in the hAEC and exosome groups, and that the LVEDD and LVESD were higher in the control group (P

Yu Cui,1,2 Nan-Nan Zhang,1 Dan Wang,1 Wei-Hong Meng,2 Hui-Sheng Chen1 1Department of Neurology, General Hospital of Northern Theater Command, Shenyang, People’s Republic of China; 2Department of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, People’s Republic of ChinaCorrespondence: Hui-Sheng Chen, Department of Neurology, General Hospital of Northern Theater Command, Shenyang, People’s Republic of China, Email chszh@aliyun.com Wei-Hong Meng, Department of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China, Email meng.weihong@qq.comBackground: Galectin-3 acts as a mediator of microglial inflammatory response following stroke injury. However, it remains unclear whether inhibiting galectin-3 protects against cerebral ischemia/reperfusion injury. We aimed to investigate the neuroprotective effects of modified citrus pectin (MCP, a galectin-3 blocker) in ischemic stroke and underlying mechanisms.Methods: The middle cerebral artery occlusion/reperfusion (MCAO/R) model in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation (ODG/R) model in neuronal (HT-22) and microglial (BV-2) cells were utilized in the following experiments: 1) the neuroprotective effects of MCP with different concentrations were evaluated in vivo and in vitro through measuring neurological deficit scores, brain water content, infarction volume, cell viability, and cell apoptosis; 2) the mechanisms of its neuroprotection were explored in mice and microglial cells through detecting the expression of NLRP3 (NOD-like receptor 3) inflammasome-related proteins by immunofluorescence staining and Western blotting analyses.Results: Among the tested concentrations, 800 mg/kg/d MCP in mice and 4 g/L MCP in cells, respectively, showed in vivo and in vitro neuroprotective effects on all the tests, compared with vehicle group. First, MCP significantly reduced neurological deficit scores, brain water content and infarction volume, and alleviated cell injury in the cerebral cortex of MCAO/R model. Second, MCP increased cell viability and reduced cell apoptosis in the neuronal OGD/R model. Third, MCP blocked galectin-3 and decreased the expression of TLR4 (Toll-like receptor 4)/NF-κBp65 (nuclear factor kappa-B)/NLRP3/cleaved-caspase-1/IL-1β (interleukin-1β) in microglial cells.Conclusion: This is the first report that MCP exerts neuroprotective effects in ischemic stroke through blocking galectin-3, which may be mediated by inhibiting the activation of NLRP3 inflammasome via TLR4/NF-κB signaling pathway in microglia.Keywords: cerebral ischemia/reperfusion injury, microglia, galectin-3, modified citrus pectin, NLRP3 inflammasome

Low cost electrodes with high activity and stability are the key to water splitting for green hydrogen production. Herein, an efficient integrated Ni/CoFe LDH array electrocatalyst is synthesized by a one-step electrodeposition strategy. The Ni/CoFe LDH shows splendid electrocatalytic performance for water oxidation, with a low overpotential (324 mV at a 50 mA cm−2 current output), a small Tafel slope (32 mV dec−1), and excellent durability. The improved activity can be attributed to the synergy of the electronic structure fine-tuning and the hydrophilic nanostructured surface.

The burdens and trends of gastric cancer are poorly understood, especially in high-prevalence countries. Based on the Global Burden of Disease Study 2019, we analyzed the incidence, death, and possible risk factors of gastric cancer in five Asian countries, in relation to year, age, sex, and sociodemographic index. The annual percentage change was calculated to estimate the trends in age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). The highest ASIR per 100,000 person-years in 2019 was in Mongolia [44 (95% uncertainty interval (UI), 34 to 55)], while the lowest was in the Democratic People’s Republic of Korea (DPRK) [23 (95% UI, 19 to 29)]. The highest ASDR per 100,000 person-years was in Mongolia [46 (95% UI, 37 to 57)], while the lowest was in Japan [14 (95% UI, 12 to 15)]. Despite the increase in the absolute number of cases and deaths from 1990 to 2019, the ASIRs and ASDRs in all five countries decreased with time and improved sociodemographic index but increased with age. Smoking and a high-sodium diet were two possible risk factors for gastric cancer. In 2019, the proportion of age-standardized disability-adjusted life-years attributable to smoking was highest in Japan [23% (95% UI, 19 to 28%)], and the proportions attributable to a high-sodium diet were highest in China [8.8% (95% UI, 0.21 to 33%)], DPRK, and the Republic of Korea. There are substantial variations in the incidence and death of gastric cancer in the five studied Asian countries. This study may be crucial in helping policymakers to make better decisions and allocate appropriate resources.

To investigate the correlation between number of retrieved lymph nodes (rLNs) and prognosis and further ascertain the optimal number of rLNs with a beneficial survival impact in patients with pN0 colon cancer. The Surveillance, Epidemiology, and End Results (SEER) database was searched for pN0 colon cancer cases. X-Tile software and Kaplan–Meier survival analysis were applied to determine the optimal number of rLNs based on the minimal probability (P) value and the largest χ2 value. Univariate analyses and Cox proportional hazard regression model were used to investigate the relationship between rLN number and overall survival. Multiple analyses were conducted to assess the prognostic predictive ability of the identified optimal rLN cut-off value under different stratifications. Nomograms were established based on the independent prognostic factors selected by the multivariate analysis to predict 3- and 5-year overall survival rates of pN0 patients. A total of 6269 pN0 colon cancer patients who underwent surgical therapy were finally included for analysis. Harvest of at least 18 lymph nodes was determined as the optimal rLN number. This cut-off rLN value ( rLNs ≥ 12 versus rLNs ≥ 18) stratified into several groups. The number of rLNs was identified as an independent prognostic factor for pN0 colon cancer. Retrieval of at least 18 lymph nodes was associated with favorable prognosis in patients with pN0 colon cancer, and should, therefore, be regarded as an alternative cut-off value for survival analysis.

We report FeOOH supported on Ni foam which enables highly efficient UOR electrocatalysis and can be readily produced through a hydrolysis reaction. Our developed UOR catalyst as the anode can provide a current density of 200 mA cm−2 at 1.427 V vs. RHE, as well as remarkable operational stability, representing the best yet reported noble metal-free urea electrolyser.

Non-natural PIM epitope Ac2PIM2 was presented by CD1b to active T cell to release IFN-γ.

Objective: To study the effects of resveratrol on apoptosis of rat brain during ischemiareperfusion and on NLRP3 inflammatory bodies, Caspase-1 and ZO-1 in microglia. Methods: According to the random digital table method, forty-five male Sprague-Dawley rats were divided into the sham-operated group (blank control group), cerebral ischemia-reperfusion group (IR control group) and resveratrol treatment group, with 15 rats in each group. After the establishment of cerebral ischemia-reperfusion model by suture method, the effects of different methods on the expression of apoptosis-related molecules (promoters, suppressors) in brain tissue, microglial NLRP3 inflammatory bodies, Caspase-1 and ZO-1 in SD rats were compared. Results: The content of apoptosis-related molecules (CytC, AIF, Caspase-8, Caspase-9, Fas, FasL) in the sham-operated group was significantly lower than that in IR control group and resveratrol group, and the content in IR control group was significantly higher than that in resveratrol group (P

Real-time BTEX(including benzene, toluene, ethylbenzene

Background: Evidence for estimating and predicting the temporal trends of gastric cancer in different age groups is lacking. Methods: Data of early-, intermediate-, and later-onset gastric cancer (EOGC, IOGC, LOGC) was from the Global Burden of Diseases Study 2019. The incidences and deaths due to EOGC, IOGC, and LOGC were analyzed by period, sex, geographic location, and sociodemographic incidence. Temporal trends were evaluated by estimated annual percentage changes (EAPCs). The incidences and temporal trends were predicted until 2035. Results: There were substantial differences in the incidence and death rates of the three populations at global, regional and national levels in 2019. From 1990 to 2019, EOGC (EAPC, −0.84) showed a slower decrease in incidence rate worldwide than IOGC (EAPC, −1.77) and LOGC (EAPC, −1.10), whereas EOGC and LOGC showed slower decreases in mortality than IOGC. The worldwide incidence rate of EOGC (EAPC, 1.44) was predicted to increase substantially from 2020 to 2035, while that for LOGC (EAPC, 0.43) was predicted to increase slightly and that for IOGC (EAPC, −0.01) was predicted to remain stable over the same period. Conclusions: This study revealed differences in the burdens and temporal trends of EOGC, IOGC, and LOGC, and highlighted the importance of tailored cancer-control measures in neglected subpopulations, especially in patients with EOGC.

BACKGROUND: Lymph node ratio (LNR) has advantages in predicting prognosis compared with American Joint Committee on Cancer (AJCC) pathological N stage. However, the prognostic value of a novel T stage-lymph node ratio (TLNR) classification for colon cancer combining LNR and pathological primary tumor stage (T stage) is currently unknown. METHODS: We included 62,294 patients with stage I–III colon cancer from the Surveillance, Epidemiology, and End Results Program as a training cohort. External validation was performed in 3,327 additional patients. A novel LNR stage was established and combined with T stage in a novel TLNR classification. Patients with similar survival were grouped according to T and LNR stages, with T1LNR1 as a reference. RESULTS: We developed a novel TLNR classification as follows: stages I (T1LNR1-2, T1LNR4), IIA (T1LNR3, T2LNR1-2, T3LNR1), IIB (T1LNR5, T2LNR3-4, T3LNR2, T4aLNR1), IIC (T2LNR5, T3LNR3-4, T4aLNR2, T4bLNR1), IIIA (T3LNR5, T4aLNR3-4, T4bLNR2), IIIB (T4aLNR5, T4bLNR3-4), and IIIC (T4bLNR5). In the training cohort, the novel TLNR classification had better prognostic discrimination (area under receiver operating characteristic curve, 0.621 vs. 0.608, two-sided P

Retraction of 'Chemical synthesis and antigenic activity of a phosphatidylinositol mannoside epitope from Mycobacterium tuberculosis' by Shi-Yuan Zhao et al., Chem. Commun., 2020, 56, 14067-14070, DOI: 10.1039/D0CC05573E.

Purpose Lymph node ratio (LNR) has advantages in predicting prognosis over the American Joint Committee on Cancer (AJCC) N stage. However, the prognostic value of establishing a novel T stage-Lymph Node Ratio classification (TLNR) for colon cancer by combining LNR and T stage is currently unknown.Methods We included 62,294 stage I-III colon cancer patients from the SEER data base as a training cohort. An external validation was performed in 3,327 additional patients. A novel LNR stage was established and included into a novel TLNR classification by combining with T stage. Patients with similar survivals were grouped according to T and LNR stages, with T1LNR1 as a reference. Results We developed a novel TLNR classification: stages I (T1LNR1-2, T1LNR4), IIA (T1LNR3, T2LNR1-2, T3LNR1), IIB (T1LNR5, T2LNR3-4, T3LNR2, T4aLNR1), IIC (T2LNR5, T3LNR3-4, T4aLNR2, T4bLNR1), IIIA (T3LNR5, T4aLNR3-4, T4bLNR2), IIIB (T4aLNR5, T4bLNR3-4), and IIIC (T4bLNR5). In the training cohort, the TLNR had better prognostic discrimination [area under receiver operating characteristic curve (AUC), 0.621 vs. 0.608, P < 0.001], superior model-fitting ability in predicting overall survival [Akaike information criteria (AIC), 561,129 vs. 562,052], and better net benefits than the AJCC 8th tumor/node/metastasis (TNM) classification. Those results were successfully validated in predicting both overall and disease-free survivals in an independent validation set. Conclusions The TLNR classification has better prognostic discrimination, model-fitting ability and net benefits than the AJCC 8th TNM classification for better stratifying operable colon cancer patients, especially in patients with less than 12 retrieved lymph nodes.

Background: It remains controversial as to which pathological classification is most valuable in predicting overall survival (OS) in patients with gastric cancer (GC). We assessed the prognostic performances of three pathological classifications in GC and developed a novel prognostic nomogram individually predicting OS. Methods: Patients were identified from the Surveillance, Epidemiology and End Results program. Univariate and multivariate analyses were performed to identify the independent prognostic factors. Model discrimination and model-fitting were evaluated by receiver operating characteristic curves and Akaike information criteria. Decision curve analysis was performed to assess clinical usefulness. The independent prognostic factors identified by multivariate analysis were further applied to develop a novel prognostic nomogram. Results: A total of 2,718 eligible GC patients were identified. The modified Lauren classification was identified as one of the independent prognostic factors of OS. It showed superior model discriminative ability and model-fitting performance over the other pathological classifications, and similar results were obtained in various patient settings. In addition, it showed superior net benefits over the Lauren classification and tumor differentiation grade in predicting 3- and 5-year OS. A novel prognostic nomogram incorporating the modified Lauren classification showed superior model discriminative ability, model-fitting performance, and net benefits over the American Joint Committee on Cancer (AJCC) 8th Edition TNM classification. Conclusion: The modified Lauren classification showed superior net benefits over the Lauren classification and tumor differentiation grade in predicting OS. A novel prognostic nomogram incorporating the modified Lauren classification showed good model discriminative ability, model-fitting performance, and net benefits.

BACKGROUND It remains controversial as to which pathological classification is most valuable in predicting the overall survival (OS) of patients with gastric cancer (GC). AIM To assess the prognostic performances of three pathological classifications in GC and develop a novel prognostic nomogram for individually predicting OS. METHODS Patients were identified from the Surveillance, Epidemiology, and End Results program. Univariate and multivariate analyses were performed to identify the independent prognostic factors. Model discrimination and model fitting were evaluated by receiver operating characteristic curves and Akaike information criteria. Decision curve analysis was performed to assess clinical usefulness. The independent prognostic factors identified by multivariate analysis were further applied to develop a novel prognostic nomogram. RESULTS A total of 2718 eligible GC patients were identified. The modified Lauren classification was identified as one of the independent prognostic factors for OS. It showed superior model discriminative ability and model-fitting performance over the other pathological classifications, and similar results were obtained in various patient settings. In addition, it showed superior net benefits over the Lauren classification and tumor differentiation grade in predicting 3- and 5-year OS. A novel prognostic nomogram incorporating the modified Lauren classification showed superior model discriminative ability, model-fitting performance, and net benefits over the American Joint Committee on Cancer 8th edition tumor-node-metastasis classification. CONCLUSION The modified Lauren classification shows superior net benefits over the Lauren classification and tumor differentiation grade in predicting OS. A novel prognostic nomogram incorporating the modified Lauren classification shows good model discriminative ability, model-fitting performance, and net benefits.

The water oxidation reaction plays a major role in many alternative-energy systems because it provides the electrons and protons required for the use of renewable electricity. We report the tuning of the iron molybdate (FeMoO4) electron structure via a coupled interface between the catalytic centers and the substrate. Our developed FeMoO4 catalysts can provide a 50 mA cm-2 current density at 1.506 V vs. RHE with excellent stability in 1.0 M KOH. The improved performance can be ascribed to the synergy of the optimized electronic structures and hierarchical nanostructure.

Background Heart failure with preserved ejection fraction (HFpEF) is a difficult disease with high morbidity and mortality rates and lacks an effective treatment. Here, we report the therapeutic effect of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), on hypertension + hyperlipidemia-induced HFpEF in a pig model. Methods HFpEF pigs were established by infusing a combination of deoxycorticosterone acetate (DOCA) and angiotensin II (Ang II), and Western diet (WD) feeding for 18 weeks. In the 9th week, half of the HFpEF pigs were randomly assigned to receive additional dapagliflozin treatment (10 mg/day) by oral gavage daily for the next 9 weeks. Blood pressure, lipid levels, echocardiography and cardiac hemodynamics for cardiac structural and functional changes, as well as epinephrine and norepinephrine concentrations in the plasma and tissues were measured. After sacrifice, cardiac fibrosis, the distribution of tyrosine hydroxylase (TH), inflammatory factors (IL-6 and TNF-α) and NO-cGMP-PKG pathway activity in the cardiovascular system were also determined. Results Blood pressure, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) were markedly increased in HFpEF pigs, but only blood pressure was significantly decreased after 9 weeks of dapagliflozin treatment. By echocardiographic and hemodynamic assessment, dapagliflozin significantly attenuated heart concentric remodeling in HFpEF pigs, but failed to improve diastolic function and compliance with the left ventricle (LV). In the dapagliflozin treatment group, TH expression and norepinephrine concentration in the aorta were strongly mitigated compared to that in the HFpEF group. Moreover, inflammatory cytokines such as IL-6 and TNF-α in aortic tissue were markedly elevated in HFpEF pigs and inhibited by dapagliflozin. Furthermore, the reduced expression of eNOS and the PKG-1 protein and the cGMP content in the aortas of HFpEF pigs were significantly restored after 9 weeks of dapagliflozin treatment. Conclusion 9 weeks of dapagliflozin treatment decreases hypertension and reverses LV concentric remodeling in HFpEF pigs partly by restraining sympathetic tone in the aorta, leading to inhibition of the inflammatory response and NO-cGMP-PKG pathway activation.