A nomogram for predicting survival of head and neck mucosal melanoma.

OBJECTIVES: We aimed to understand the clinical characteristics and better predict the prognosis of patients with mucosal melanoma of the head and neck (MMHN) using a nomogram. METHODS: Three hundred patients with nometastatic MMHN were included. Multivariable Cox regression was performed to analyze independent prognostic factors for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS), and these factors were used to develop a nomogram. Concordance indexes (C-indexes), calibration plots, and receiver operating characteristic (ROC) analysis were performed to test the predictive performance of the nomogram in both the primary (n = 300) and validation cohorts (n = 182). RESULTS: The primary tumor site, T stage and N stage were independent risk factors for survival and were included in the nomogram to predict the 3- and 5-year OS, DFS, DMFS, and LRRFS in the primary cohort. The C-indexes (both > 0.700), well-fit calibration plots, and area under the ROC curve (both > 0.700) indicated the high diagnostic accuracy of the nomogram, in both the primary and validation cohorts. The patients were divided into three groups (high-risk, intermediate-risk, and low-risk groups) according to their nomogram scores. The survival curves of OS, DFS, DMFS, and LRRFS were well separated by the risk groups in both cohorts (all P < 0.001). CONCLUSIONS: The nomogram can stratify MMHN patients into clinically meaningful taxonomies to provide individualized treatment.

Self-Perpetuating Carbon Foam Microwave Plasma Conversion of Hydrocarbon Wastes into Useful Fuels and Chemicals.

White wastes (unseparated plastics, face masks, textiles, etc.) pose a serious challenge to sustainable human development and the ecosystem and have recently been exacerbated due to the surge in plastic usage and medical wastes from COVID-19. Current recycling methods such as chemical recycling, mechanical recycling, and incineration require either pre-sorting and washing or releasing CO2. In this work, a carbon foam microwave plasma process is developed, utilizing plasma discharge to generate surface temperatures exceeding ∼3000 K in a N2 atmosphere, to convert unsorted white wastes into gases (H2, CO, C2H4, C3H6, CH4, etc.) and small amounts of inorganic minerals and solid carbon, which can be buried as artificial "coal". This process is self-perpetuating, as the new solid carbon asperities grafted onto the foam's surface actually increase the plasma discharge efficiency over time. This process has been characterized by in situ optical probes and infrared sensors and optimized to handle most of the forms of white waste without the need for pre-sorting or washing. Thermal measurement and modeling show that in a flowing reactor, the device can achieve locally extremely high temperatures, but the container wall will still be cold and can be made with cheap materials, and thus, a miniaturized waste incinerator is possible that also takes advantage of intermittent renewable electricity.

Cyclic deformation leads to defect healing and strengthening of small-volume metal crystals.

When microscopic and macroscopic specimens of metals are subjected to cyclic loading, the creation, interaction, and accumulation of defects lead to damage, cracking, and failure. Here we demonstrate that when aluminum single crystals of submicrometer dimensions are subjected to low-amplitude cyclic deformation at room temperature, the density of preexisting dislocation lines and loops can be dramatically reduced with virtually no change of the overall sample geometry and essentially no permanent plastic strain. This "cyclic healing" of the metal crystal leads to significant strengthening through dramatic reductions in dislocation density, in distinct contrast to conventional cyclic strain hardening mechanisms arising from increases in dislocation density and interactions among defects in microcrystalline and macrocrystalline metals and alloys. Our real-time, in situ transmission electron microscopy observations of tensile tests reveal that pinned dislocation lines undergo shakedown during cyclic straining, with the extent of dislocation unpinning dependent on the amplitude, sequence, and number of strain cycles. Those unpinned mobile dislocations moving close enough to the free surface of the thin specimens as a result of such repeated straining are then further attracted to the surface by image forces that facilitate their egress from the crystal. These results point to a versatile pathway for controlled mechanical annealing and defect engineering in submicrometer-sized metal crystals, thereby obviating the need for thermal annealing or significant plastic deformation that could cause change in shape and/or dimensions of the specimen.

Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning.

BACKGROUND/AIMS: Previous studies have shown that heat shock protein 90 (HSP90)-mediated mitochondrial import of connexin 43 (Cx43) is critical in preconditioning cardioprotection. The present study was designed to test whether postconditioning has the same effect as preconditioning in promoting Cx43 translocation to mitochondria and whether mitochondrial HSP90 modulates this effect. METHODS: Cellular models of hypoxic postconditioning (HPC) from rat heart-derived H9c2 cells and neonatal rat cardiomyocytes were employed. The effects of HPC on cardiomyocytes apoptosis were examined by flow cytometry and Hoechst 33342 fluorescent staining. Reactive oxidative species (ROS) production was assessed with the peroxide-sensitive fluorescent probe 2',7'-dichlorofluorescin in diacetate (DCFH-DA). The anti- and pro-apoptotic markers Bcl-2 and Bax, HSP90 and Cx43 protein levels were studied by Western blot analysis in total cell homogenate and sarcolemmal and mitochondrial fractions. The effects on HPC of the HSP90 inhibitor geldanamycin (GA), ROS scavengers superoxide dismutase (SOD) and catalase (CAT), and small interfering RNA (siRNA) targeting Cx43 and HSP90 were also investigated. RESULTS: HPC significantly reduced hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis. These beneficial effects were accompanied by an increase in Bcl-2 levels and a decrease in Bax levels in both sarcolemmal and mitochondrial fractions. HPC with siRNA targeting Cx43 or the ROS scavengers SOD plus CAT significantly prevented ROS generation and HPC cardioprotection, but HPC with either SOD or CAT did not. These data strongly supported the involvement of Cx43 in HPC cardioprotection, likely via modulation of the ROS balance which plays a central role in HPC protection. Furthermore, HPC increased total and mitochondrial levels of HSP90 and the mitochondria-to-sarcolemma ratio of Cx43; blocking the function of HSP90 with the HSP90 inhibitor geldanamycin (GA) or siRNA targeting HSP90 prevented the protection of HPC and the HPC-induced association of Cx43, indicating that mitochondrial HSP90 was important for mitochondrial translocation of Cx43 during HPC. CONCLUSION: Mitochondrial HSP90 played a central role in HPC cardioprotection, and its activity was linked to the mitochondrial targeting of Cx43, the activation of which triggered ROS signaling and the subsequent reduction of redox stress. Consequently, its target gene, Bcl-2, was upregulated, and proapoptotic Bax was inhibited in the sarcolemma and mitochondria, ultimately attenuating H/R-induced cardiomyocyte apoptosis. These data reveal a novel mechanism of HPC protection.

In Situ Observation on Dislocation-Controlled Sublimation of Mg Nanoparticles.

Sublimation is an important endothermic phase transition in which the atoms break away from their neighbors in the crystal lattice and are removed into the gas phase. Such debonding process may be significantly influenced by dislocations, the crystal defect that changes the bonding environment of local atoms. By performing systematic defects characterization and in situ transmission electron microscopy (TEM) tests on a core--shell MgO-Mg system, which enables us to "modulate" the internal dislocation density, we investigated the role of dislocations on materials' sublimation with particular focus on the sublimation kinetics and mechanism. It was observed that the sublimation rate increases significantly with dislocation density. As the density of screw dislocations is high, the intersection of screw dislocation spirals creates a large number of monatomic ledges, resulting in a "liquid-like" motion of solid-gas interface, which significantly deviates from the theoretically predicted sublimation plane. Our calculation based on density functional theory demonstrated that the remarkable change of sublimation rate with dislocation density is due to the dramatic reduction in binding energy of the monatomic ledges. This study provides direct observation to improve our understanding on this fundamental phase transition as well as to shed light on tuning materials' sublimation by "engineering" dislocation density in applications.

Surface Rebound of Relativistic Dislocations Directly and Efficiently Initiates Deformation Twinning.

Under ultrahigh stresses (e.g., under high strain rates or in small-volume metals) deformation twinning (DT) initiates on a very short time scale, indicating strong spatial-temporal correlations in dislocation dynamics. Using atomistic simulations, here we demonstrate that surface rebound of relativistic dislocations directly and efficiently triggers DT under a wide range of laboratory experimental conditions. Because of its stronger temporal correlation, surface rebound sustained relay of partial dislocations is shown to be dominant over the conventional mechanism of thermally activated nucleation of twinning dislocations.

Novel functional role of heat shock protein 90 in protein kinase C-mediated ischemic postconditioning.

BACKGROUND: Previous studies have shown that heat shock protein 90 (HSP90) plays a vital role in ischemic preconditioning. The present study was designed to explore whether HSP90 might be responsible for cardioprotection in ischemic postconditioning (PostC). MATERIALS AND METHODS: Rat hearts underwent 30 min of regional ischemia and 2 h of reperfusion in situ, and PostC was effected with three cycles of 30-s reperfusion and 30-s coronary artery occlusion at the end of ischemia. Ninety rats were randomized into five groups: sham; ischemia-reperfusion (I/R); PostC; 1 mg/kg HSP90 inhibitor geldanamycin (GA) plus PostC (PostC + GA1); and 5 mg/kg GA plus PostC (PostC + GA5). The GA was administered 10 min before reperfusion. RESULTS: Compared with the I/R group, the PostC group exhibited lower infarct size (46.7 ± 3.0% versus 27.4 ± 4.0%, respectively), release of lactate dehydrogenase and creatine kinase-MB (2252.6 ± 350.8 versus 1713.7 ± 202.4 IU/L, 2804.3 ± 315.7 versus 1846.2 ± 238.0 IU/L, respectively), cardiomyocyte apoptosis (48.4 ± 5.6% versus 27.6 ± 3.8%, respectively), and mitochondrial damage. These beneficial effects were accompanied by an increase in mitochondrial Bcl-2 levels and a decrease in Bax levels. In addition, mitochondrial protein kinase Cepsilon (PKCepsilon) was relatively low in the I/R group but significantly higher in the PostC group, whereas cytosolic PKCepsilon was relatively high in the I/R group but significantly lower in the PostC group, suggesting the translocation of PKCepsilon from cytosol to mitochondria during PostC. However, blocking HSP90 function with GA inhibited the protection of PostC and PKCepsilon mitochondrial translocation. CONCLUSIONS: HSP90 is critical in PostC-induced cardioprotection, and its activity might be linked to mitochondrial targeting of PKCepsilon, the activation of which results in upregulation of its target gene, Bcl-2, and the inhibition of proapoptotic Bax in mitochondria.

Oral chemotherapy versus observation alone in nasopharyngeal carcinoma patients with persistently detected circulating cell-free Epstein-Barr virus DNA during follow-up.

AIM: Despite the high risk of tumor recurrence, patients with nasopharyngeal carcinoma (NPC) with persistently (at least twice) detected circulating cell-free Epstein-Barr virus (EBV) DNA levels during follow-up are routinely recommended to keep observation. For these patients, whether administering more aggressive treatment could improve survival outcomes remains unknown. MATERIALS AND METHODS: We retrospectively included 431 patients with nonmetastatic NPC with persistently detected EBV DNA during follow-up, who do not have clinical or imaging evidence of recurrence. Among these patients, 79 were administered oral chemotherapy, and the remaining 352 underwent observation alone. Baseline characteristics were balanced with propensity score matching (PSM) analysis. The primary endpoint was modified disease-free survival (mDFS), defined as time from detectable EBV DNA result to tumor recurrence or death. The secondary endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: One-to-three PSM resulted in 251 eligible patients (oral chemotherapy group, 73; observation group, 178). In the matched cohort, the oral chemotherapy group had higher median mDFS (12.9 months [95 % confidence interval [CI] 9.6-16.3] vs. 6.8 months [95 % CI 5.8-7.8], p = 0.009) and DFS (24.1 months [95 % CI 18.5-29.7] vs. 16.7 months [95 % CI 14.4-19.1], p = 0.035) than the observation group. The median OS was numerically higher in the oral chemotherapy group than in the observation group (57.9 months [95 % CI 42.5-73.3] vs. 50.8 months [95 % CI 39.7-61.9], p = 0.71). A consistent benefit favoring oral chemotherapy was observed for mDFS in all subgroups analyses for male, <45 years, stage III-IVa disease, pretreatment EBV DNA load ≥ 4,000 copies/mL, no induction chemotherapy, or a detectable EBV DNA load ≥ 1,200 copies/mL. After adjusting for other confounders in the multivariate analysis, oral chemotherapy remained a significantly favorable factor for both mDFS (hazard ratio [HR] 0.67, 95 % CI 0.50-0.89; p = 0.006) and DFS (HR 0.68, 95 % CI 0.51-0.91; p = 0.01), but not a significant factor for OS (HR 0.89, 95 % CI 0.62-1.27; p = 0.52). CONCLUSIONS: In patients with NPC having persistently detected EBV DNA levels but without clinical or imaging evidence of recurrence during follow-up, oral chemotherapy significantly prolongs mDFS and DFS. Employing oral chemotherapy as a more aggressive treatment option, as opposed to mere observation, could potentially benefit these patients, although further prospective validation is necessitated.

DCAF7 Acts as A Scaffold to Recruit USP10 for G3BP1 Deubiquitylation and Facilitates Chemoresistance and Metastasis in Nasopharyngeal Carcinoma.

Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma.

Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients' survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.

A radiogenomic clinical decision support system to inform individualized treatment in advanced nasopharyngeal carcinoma.

Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.

A New Zinc Salt Chemistry for Aqueous Zinc-Metal Batteries.

Aqueous zinc-ion batteries (ZIBs) are promising energy storage solutions with low cost and superior safety, but they suffer from chemical and electrochemical degradations closely related to the electrolyte. Here, a new zinc salt design and a drop-in solution for long cycle-life aqueous ZIBs are reported. The salt Zn(BBI)2 with a rationally designed anion group, N-(benzenesulfonyl)benzenesulfonamide (BBI- ), has a special amphiphilic molecular structure, which combines the benefits of hydrophilic and hydrophobic groups to properly tune the solubility and interfacial condition. This new zinc salt does not contain fluorine and is synthesized via a high-yield and low-cost method. It is shown that 1 m Zn(BBI)2 aqueous electrolyte with a widened cathodic stability window effectively stabilizes Zn metal/H2 O interface, mitigates chemical and electrochemical degradations, and enables both symmetric and full cells using a zinc-metal electrode.

Prognostic value of the immunohistochemical score based on four markers in head and neck squamous cell carcinoma.

Purpose: Head and neck squamous cell carcinoma (HNSCC) ranks sixth among all cancers globally regarding morbidity, and it has a poor prognosis, high mortality, and highly aggressive properties. In this study, we established a model for predicting prognosis based on immunohistochemical (IHC) scores. Methods: Data on 402 HNSCC cases were collected, the glmnet Cox proportional hazards model was used, risk factors were analyzed for predicting the prognosis of survival, and the IHC score was established. We used the IHC score to predict disease-free survival (DFS) using training and independent validation cohorts, including 264 cases in total. Additionally, the accuracy of the IHC score and the TNM system (8th edition) was compared. A DFS prediction nomogram was established by combining the prognostic factors. Results: The IHC scores included CK, Ki-67, p16, and p40 staining intensity. The concordance index and the Kaplan-Meier survival analysis showed that the IHC scores had high predictive power for HNSCC. Our results showed that the IHC score is an independent factor that can predict prognosis in a multivariate Cox regression analysis. When predicting DFS, the IHC score had a significantly higher value for the area under the ROC curve (AUC) than that of the TNM system. A nomogram was established and included the IHC score, age, tumor location, and the TNM stage. The calibration curves exhibited high consistency between the prognosis predicted by our nomogram and the actual prognosis. Conclusions: The IHC score was more accurate than the eighth edition of the TNM system in predicting HNSCC prognosis. Therefore, combining the two methods can facilitate individualized patient consultation and care.

TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models.

Although radiotherapy can promote antitumour immunity, the mechanisms underlying this phenomenon remain unclear. Here, we demonstrate that the expression of the E3 ubiquitin ligase, tumour cell-intrinsic tripartite motif-containing 21 (TRIM21) in tumours, is inversely associated with the response to radiation and CD8+ T cell-mediated antitumour immunity in nasopharyngeal carcinoma (NPC). Knockout of TRIM21 modulates the cGAS/STING cytosolic DNA sensing pathway, potentiates the antigen-presenting capacity of NPC cells, and activates cytotoxic T cell-mediated antitumour immunity in response to radiation. Mechanistically, TRIM21 promotes the degradation of the mitochondrial voltage-dependent anion-selective channel protein 2 (VDAC2) via K48-linked ubiquitination, which inhibits pore formation by VDAC2 oligomers for mitochondrial DNA (mtDNA) release, thereby inhibiting type-I interferon responses following radiation exposure. In patients with NPC, high TRIM21 expression was associated with poor prognosis and early tumour relapse after radiotherapy. Our findings reveal a critical role of TRIM21 in radiation-induced antitumour immunity, providing potential targets for improving the efficacy of radiotherapy in patients with NPC.

[The effect of mitochondrial oxidative stress and the expression of Bcl-2 and Bax proteins on cardiomyocyte apoptosis during hypoxia postconditioning].

OBJECTIVE: To investigate mitochondrial oxidative stress on cardiomyocyte apoptosis and the expression of Bcl-2 and Bax proteins in cardiac sarcolemma and mitochondria after application of hypoxia postconditioning and free radical scavengers. METHODS: Primary cultured neonatal rat cardiomyocytes were exposed to 3 h hypoxia (H) followed by (1) 6 h of reoxygenation (R) (H/R), (2) 3 intermittent cycles of 5 min H and R before 6 h of R (PC), (3) application of superoxide dismutase (SOD) before PC (SOD+PC), (4) application of catalase (CAT) before PC (CAT+PC), and (5) application of SOD plus CAT before PC (SOD+CAT+PC). Cardiac sarcolemma and mitochondria were isolated by differential centrifugation. Mitochondrial reactive oxygen species (ROS) was detected with fluorescent probes (DCFH-DA) and cardiomyocyte apoptosis was detected with flow cytometry. The expressions of Bcl-2 and Bax proteins in cardiac sarcolemma and mitochondria were measured by Western blot. RESULTS: Mitochondrial ROS reduced significantly in PC, SOD+PC, CAT+PC and especially in SOD+CAT+PC groups (all P<0.01). The number of apoptotic cardiomyocytes reduced significantly in PC, SOD+PC and CAT+PC (all P<0.01) but not in SOD+CAT+PC groups. Bcl-2 levels increased while Bax levels decreased in cardiac sarcolemma and mitochondria in PC, SOD+PC and CAT+PC groups (all P<0.01), Bcl-2 levels decreased and Bax levels increased in H/R and PC+SOD+CAT groups (all P<0.01). CONCLUSIONS: PC attenuated H/R induced ROS and cardiomyocyte apoptosis, which might be mediated by upregulating the expression of Bcl-2 and downregulating the Bax in mitochondria and sarcolemma; SOD or CAT alone did not but SOD plus CAT attenuate the anti-apoptotic effect of hypoxia postconditioning; mitochondrial ROS thus plays an important role in PC's cardioprotection.

Validation of a modified Chinese version of Mini-Addenbrooke's Cognitive Examination for detecting mild cognitive impairment.

BACKGROUND: For detecting mild cognitive impairment (MCI), brief cognitive screening tools are increasingly required for the advantage of time saving and no need for special equipment or trained raters. We aimed to develop a modified Chinese version of Mini-Addenbrooke's Cognitive Examination (C-MACE) and further evaluate its validation in detecting MCI. METHODS: A total of 716 individuals aged from 50 to 90 years old were recruited, including 431 cognitively normal controls (NC) and 285 individuals with MCI. The effect size of Cramer's V was used to explore which items in the Chinese version of Addenbrooke's Cognitive Examination-III (ACE-III-CV) best associated with MCI and to form the C-MACE. Receiver operating characteristic (ROC) analyses were carried out to explore the ability of C-MACE, ACE-III-CV, Chinese version of Montreal Cognitive Assessment-Basic (MoCA-BC), and Mini-Mental State Examination (MMSE) in discriminating MCI from NC. RESULTS: Five items with greatest effect sizes of Cramer's V were selected from ACE-III-CV to form the C-MACE: Memory Immediate Recall, Memory Delayed Recall, Memory Recognition, Verbal Fluency Animal and Language Naming. With a total score of 38, the C-MACE had a satisfactory classification accuracy in detecting MCI (area under the ROC curve, AUC = 0.892), superior to MMSE (AUC = 0.782) and comparable to ACE-III-CV (AUC = 0.901) and MoCA-BC (AUC = 0.916). In the subgroup of Age > 70 years, Education ≤ 12 years, the C-MACE got a highest classification accuracy (AUC = 0.958) for detecting MCI. CONCLUSION: In the Chinese-speaking population, C-MACE derived from ACE-III-CV may identify MCI with a good classification accuracy, especially in aged people with low education.

Chinese herbal formula shen-ling-bai-zhu-san to treat chronic gastritis: Clinical evidence and potential mechanisms.

BACKGROUND: Chronic gastritis (CG) is an inflammatory disease of the gastric mucosa. Shen-ling-bai-zhu san (SLBZS), a traditional Chinese medicine formula, is widely used for treating CG. Nevertheless, its effects are currently unclear. AIM: To determine the clinical evidence and potential mechanisms of SLBZS for the treatment of CG. METHODS: We systematically searched 3 English (PubMed, Embase, Medline) and 4 Chinese databases (Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform, and the VIP information resource integration service platform) without language or publication bias restriction. Qualified studies were selected according to pre-set inclusion and exclusion criteria. RevMan 5.3 software was used for meta-analysis and literature quality assessment, Stata 14.0 software was used for sensitivity analysis, GRADE profiler 3.6 was used to evaluate the quality of evidence. And then, network pharmacology analysis was applied to primary research the mechanisms of action of SLBZS on CG. RESULTS: Fourteen studies were finally included, covering 1335 participants. Meta-analysis indicated that: (1) SLBZS was superior to conventional therapies [risk ratio (RR): 1.29, 95% confidence interval (CI): 1.21 to 1.37, P < 0.00001]; (2) SLBZS was better than conventional therapies [RR: 0.24, 95% confidence interval (95%CI): 0.11 to 0.55, P = 0.0007] in terms of recurrence rate and reversal of Helicobacter pylori positivity (RR: 1.20, 95%CI: 1.11 to 1.30, P < 0.00001); and (3) The safety of SLBZS for CG remains unclear. According to the GRADE method, the quality of evidence was not high. Besides, SNZJS might treat CG by acting on related targets and pathways such as EGFR tyrosine kinase inhibitor resistance, the PI3K-Akt signaling pathway, and others. CONCLUSION: SLBZS might be useful in treating CG, but long-term effects and specific clinical mechanisms of it maintain unclear. More samples and high-quality clinical experiments should be assessed and verified in the next step.

Modeling LiF and FLiBe Molten Salts with Robust Neural Network Interatomic Potential.

Lithium-based molten salts have attracted significant attention due to their applications in energy storage, advanced fission reactors, and fusion devices. Lithium fluorides and particularly 66.6%LiF-33.3%BeF2 (Flibe) are of considerable interest in nuclear systems, as they show an excellent combination of favorable heat transfer, neutron moderation, and transmutation characteristics. For nuclear salts, the range of possible local structures, compositions, and thermodynamic conditions presents significant challenges in atomistic modeling. In this work, we demonstrate that atom-centered neural network interatomic potentials (NNIPs) provide a fast method for performing molecular dynamics of molten salts that is as accurate as ab initio molecular dynamics. For LiF, these potentials are able to accurately reproduce ab initio interactions of dimers, crystalline solids under deformation, crystalline LiF near the melting point, and liquid LiF at high temperatures. For Flibe, NNIPs accurately predict the structures and dynamics at normal operating conditions, high-temperature-pressure conditions, and in the crystalline solid phase. Furthermore, we show that NNIP-based molecular dynamics of molten salts are scalable to reach long time scales (e.g., nanosecond) and large system sizes (e.g., 105 atoms) while maintaining ab initio density functional theory accuracy and providing more than 3 orders of magnitude of computational speedup for calculating structure and transport properties.

Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting complement activation and upregulation of miR-499.

The complement system plays a vital role in myocardial ischemia/reperfusion (I/R) injury. microRNA (miR)-499 is involved in the cardioprotection of ischemic postconditioning (IPostC). The present study aimed to study the role of the complement system and miR-499 in IPostC. Rat hearts were subjected to coronary ligation for 30 min, followed by reperfusion for 2 h. IPostC was introduced at the onset of reperfusion with three cycles of reperfusion for 30 sec and coronary artery occlusion for 30 sec. To study the role of miR-499 in IPostC, adeno-associated virus (AAV) vectors of miR-499-5p (AAV-miR-499-5p) and miR-499-5p-sponge (AAV-miR-499-5p-sponge) were transfected via tail vein injection, followed by IPostC protocols. Cardiac injury as well as the status of local and systemic complement activation and inflammation were assessed. IPostC significantly attenuated I/R-induced rat cardiomyocyte apoptosis and the myocardial infarct size. These beneficial effects were accompanied by decreased local and circulating complement component (C)3a and C5a levels, decreased inflammatory marker expression, decreased NF-κB signaling and increased cardiac miR-499 expression. AAV-miR-499-5p prevented local and systemic complement activation and inflammation as well as enhanced the cardioprotection of IPostC, whereas AAV-miR-499-5p-sponge produced the opposite effects. In summary, IPostC protected the rat myocardium against I/R injury, by inhibiting local and systemic complement activation; inflammation; NF-κB signaling; and upregulation of miR-499. As such, miR-499 may have a critical role in IPostC-mediated cardioprotection against I/R injury.

A Fe3N/carbon composite electrocatalyst for effective polysulfides regulation in room-temperature Na-S batteries.

The practical application of room-temperature Na-S batteries is hindered by the low sulfur utilization, inadequate rate capability and poor cycling performance. To circumvent these issues, here, we propose an electrocatalyst composite material comprising of N-doped nanocarbon and Fe3N. The multilayered porous network of the carbon accommodates large amounts of sulfur, decreases the detrimental effect of volume expansion, and stabilizes the electrodes structure during cycling. Experimental and theoretical results testify the Fe3N affinity to sodium polysulfides via Na-N and Fe-S bonds, leading to strong adsorption and fast dissociation of sodium polysulfides. With a sulfur content of 85 wt.%, the positive electrode tested at room-temperature in non-aqueous Na metal coin cell configuration delivers a reversible capacity of about 1165 mA h g-1 at 167.5 mA g-1, satisfactory rate capability and stable capacity of about 696 mA h g-1 for 2800 cycles at 8375 mA g-1.